• The distribution of RBC lithium ratios in vitro in a recently hospitalized psychiatric population was found to be multimodal. Psychotic patients who had an antipsychotic response during open trials of lithium carbonate alone were identified with high sensitivity (89%), but low specificity (51%) before drug treatment, by lithium ratios that were in the extreme modes of the distribution (<0.30 or >0.38). Diagnostic efficiency of the test was 61%. The DSM-III diagnosis of schizophreniform disorder demonstrated 90% diagnostic efficiency in predicting response/nonresponse during treatment with lithium carbonate alone. A subgroup of the psychotic disorders was similar to affective disorders with respect to course of illness, biological characteristics, and response to lithium carbonate.