It has been suggested that inclusion of a placebo treatment arm in controlled clinical trials might bias the selection of study subjects. Presumably, patients in the placebo-controlled studies are more stable, but there are no data available to support such an assumption. The authors tested the hypothesis in a set of randomized trials of neuroleptics in treating schizophrenia by comparing placebo-controlled (PCTs) and comparator-controlled trials (CCTs) in terms of basic patient characteristics. The results, based on a total of 296 studies, showed that the patients in PCTs, compared with those in CCTs, were older (p < 0.002), had a longer duration of illness (p < 0.001), and a lower initial symptom severity (p < 0.02). No difference was found in the number of subjects per treatment arm or in the proportion of female subjects. However, investigation of studies which used same-gender study subjects revealed that female-only populations were more likely to be tested in PCTs (p < 0.03) than in CCTs. To investigate current trends in psychopharmacologic research, the authors tested separately a subset of trials of new atypical antipsychotics. The results indicated a significantly smaller number of females participating in the latest PCTs (p < 0.0003). Moreover, our findings suggest that the characteristics of patients in the current controlled trials are rather uniform; thus, the generalizability of new study findings for certain groups of patients with schizophrenia (e.g., with early or late onset or brief duration of illness) may be compromised.