Eleven consecutive schizophrenic patients with a mean duration of illness of 2.2 (range 0.9-3.8) years and early signs of resistance to conventional neuroleptics were studied prospectively in a 26-week open trial with clozapine (mean dose 192.5 mg at week 8 and 225.0 mg at end-point). Of the ten patients who completed the study, nine improved by 20% or more on total Brief Psychiatric Rating Scale (BPRS) scores; six (good responders) showed more than 30%, and four (fair responders) 21-26% improvement on total Positive and Negative Syndrome Scale (PANSS) scores. The improvement was observed mainly within the first 8 weeks. Duration of illness correlated negatively (P=0.047) with the decrease of positive PANSS scores. The duration of illness of the fair responders was more than twice that of the good responders. Clozapine appears to be a safe and effective treatment alternative for early treatment-resistant schizophrenic patients. These patients seem to respond to relatively low clozapine doses. Early rather than late transfer to clozapine in this population may be of benefit for later clinical outcome.