BACKGROUND In view of the inconclusive reports in the literature about the response to neuroleptics of chronic schizophrenics with negative symptoms, the authors further evaluated this issue. METHODS A sample of 30 ambulatory chronic schizophrenics meeting DSM-III-R criteria who had to a marked degree at least two negative symptoms of the five on the Scale for the Assessment of Negative Symptoms (SANS) received various therapeutic dosages of thiothixene for 3 months. The average dose was 26.75 mg/day. Subjects were periodically evaluated with the Brief Psychiatric Rating Scale, Negative Symptoms Rating Scale (a modified version of the SANS), and the Randt Memory Test. The time effect on treatment was calculated by repeated measures of analysis of variance. The relationship between the positive and negative symptoms was tested by an analysis of covariance. RESULTS Both negative and positive symptoms improved with treatment. The negative symptoms tended to respond to treatment predominantly independently of the positive ones. At the end of the study, 63% (N = 19) of patients had improved moderately, 16% (N = 5) had improved slightly, and 20% (N = 6) had not improved. CONCLUSIONS The data require further support from a long-term follow-up study that may show the extent to which these gains are maintained over time.