The authors examined levels of noncompliance with oral antipsychotic medication regimens and factors influencing it among 87 Ss consecutively readmitted to a hospital with an acute psychotic relapse of schizophrenia or schizoaffective disorder. Compliance was assessed using a structured clinical interview. Ss also completed a self-report questionnaire to measure insight (M. Birchwood et al, 1994) and the Drug Attitude Inventory to assess attitudes toward medication. Of the 87 Ss, the 21 Ss taking depot medication (DM) were significantly more likely than the 66 Ss (mean age 37.3 yrs) taking only oral medication (OM) to be regularly compliant. Only 22 of the 66 OM Ss were compliant vs 12 of the 21 DM Ss. 15 of the OM Ss had comorbid substance use or dependence disorders, 14 of who were irregularly compliant. Excluding Ss with current comorbid substance misuse, the 21 regularly compliant Ss had a significantly higher mean insight score than the irregularly compliant Ss. Overall, results suggest that comorbid substance misuse, negative subjective response to neuroleptics, and lack of insight contribute to noncompliance.