Several investigators have implicated a role for free radical-mediated pathology in schizophrenia. No study has ever examined the effect of vitamin C with atypical antipsychotics in the treatment of schizophrenia. The aim of this study was to examine the effect of oral vitamin C with atypical antipsychotics on serum malondialdehyde (MDA), plasma ascorbic acid levels and brief psychiatric rating scale (BPRS) score in schizophrenic patients. Forty schizophrenic patients participated in a prospective, double-blind, placebo-controlled, non-crossover, 8-week study. The patients with schizophrenia were divided randomly into placebo and vitamin C groups of 20 each. Serum MDA and plasma ascorbic acid were estimated by the methods of Nischal and Aye, respectively. Increased serum MDA and decreased plasma ascorbic acid levels were found in schizophrenic patients. These levels were reversed significantly after treatment with vitamin C along with atypical antipsychotics compared to placebo with atypical antipsychotics. BPRS change scores at 8 weeks improved statistically significantly with vitamin C as compared to placebo.