Optimal dosing of psychotherapeutic agents has implications for both symptom control and patient compliance. Trials of ziprasidone in bipolar mania and schizophrenia suggest a target dose of 120-160 mg/d and that rapid titration to this level provides maximum symptom improvement. In this report, data from 2 similarly designed fixed-dose placebo-controlled studies of ziprasidone (rapidly titrated to target doses of 40, 80, 120, or 160 mg/d) in patients with acute schizophrenia were pooled. 369 patients received ziprasidone and 171 patients received placebo. Efficacy was assessed using PANSS at Weeks 1 and 6 (LOCF endpoint) of treatment. Tolerability was assessed by discontinuations (all-cause and due to adverse events). There was a significant linear dose-response relationship between ziprasidone dose and PANSS total score (F = 12.32, P ≤ 0.001). All ziprasidone doses produced statistically significant improvement in PANSS total score; the largest effect size (0.52) was observed for the 160 mg/d group. At Week 6, least-squares mean PANSS total score decreases from baseline were 9.98, 9.54, 11.71, and 14.87 in 40, 80, 120, and 160 mg/d groups, respectively. The corresponding placebo decrease was 2.79. At Week 1, decreases from baseline were 6.18, 5.70, 7.80, and 8.96 in 40, 80, 120, and 160 mg/d groups, respectively. The corresponding placebo decrease was 0.84. Tolerability of ziprasidone 160 mg/d (all-cause/AE discontinuations at week 6: 22%/15% versus 35%/0% for placebo) was comparable with that of lower doses. Rapid titration of ziprasidone to 160 mg/d was associated with greater efficacy compared with lower doses and was well tolerated.