• Evaluate the effects of single doses of sildenafil 50 & 100 mg compared to placebo on psychotic, negative, and mood symptoms. [ Time Frame: 12 days ] [ Designated as safety issue: No ]
• Side effects of sildenafil 50 & 100 mg as self-reported by subjects and as measured with vital signs. [ Time Frame: 12 days ] [ Designated as safety issue: Yes ]

The study is a double-blind, placebo-controlled, random-order, single-dose crossover trial of sildenafil 50 & 100 mg added to stable antipsychotic treatment in schizophrenia patients to assess whether this PDE5 inhibitor improves cognitive functioning (including verbal memory, fluency, attention, spatial memory, motor speed, and executive function) and clinical symptoms (psychotic, negative, mood symptoms, and self-reports of side-effects).

Specific Aims:

1. Evaluate the effects of single doses of sildenafil 50 & 100 mg compared to placebo on cognitive functioning, including verbal memory, fluency, attention, spatial memory, motor speed, and executive function.
2. Evaluate the effects of single doses of sildenafil 50 & 100 mg compared to placebo on psychotic, negative, and mood symptoms.
3. Assess self-reports of side effects of sildenafil 50 & 100 mg.

Location and Subjects:

25 adult outpatients with schizophrenia will be recruited from the Massachusetts General Hospital outpatient clinic or the Freedom Trail Clinic of the Lindemann Center. All research procedures will be performed at the Psychopharmacology Clinic of the Massachusetts General Hospital. Subjects must be English speaking because the cognitive battery has only been validated in English.

Inclusion Criteria:

1. Diagnosis of schizophrenia, any subtype.
2. Age 18-65 years
3. Male or female
4. Clinically stable without a medication change within 4 weeks
5. Able to complete cognitive testing (must be English-speaking)
6. Willing to use appropriate birth control during study participation (if female)

Exclusion Criteria:

1. Active substance abuse or dependence
2. PDE 5 inhibitor taken within 24 hours of study drug
3. Currently taking a drug that inhibits hepatic cytochrome P450 3A4 (eg. Nefazadone, fluvoxamine, erythromycin, ketoconazole, itraconazole, cimetidine, saquinavir, ritonavir, St. John's wort, or grapefruit juice).
4. Currently taking drugs that induce P45 3A4 (eg. phenytoin, carbamezapine, Phenobarbital, rifampin)
5. Unstable medical disease
6. Significant cardiac disease
7. Bleeding disorder
8. Peptic ulcer disease
9. Hepatic impairment
10. Moderate or greater renal impairment
11. History of migraines
12. Currently taking nitrates or alpha blockers
13. Resting blood pressure < 90/50 or >140/90 mm.
14. History of intolerance to PDE5 inhibitors
15. History of inappropriate sexual behavior (eg, masturbation in public, stalking, assault)
16. History of priapism
17. Pregnant or lactating