Study Objective. To explore the clinical characteristics of hyperglycemia in patients treated with olanzapine. Design. Retrospective, epidemiologic survey of spontaneously reported adverse events related to olanzapine therapy. Setting. Government-affiliated drug evaluation center. Patients. Two hundred thirty-seven patients with olanzapine-associated diabetes or hyperglycemia. Intervention. One hundred ninety-six cases from January 1994-May 15, 2001, were identified with the United States Food and Drug Administration's MedWatch Drug Surveillance System, and 41 cases published through May 15, 2001, were identified with MEDLINE or through meeting abstracts. Measurements and Main Results. Of the 237 cases, 188 were new-onset diabetes, 44 were exacerbations of preexistent disease, and 5 could not be classified. Mean patient age for newly diagnosed cases was 40.7 ± 12.9 years and male:female ratio was 1.8. Seventy-three percent of all cases of hyperglycemia appeared within 6 months of start of olanzapine therapy. Eighty patients had metabolic acidosis or ketosis, 41 had glucose levels of 1000 mg/dl or greater, and 15 patients died. When olanzapine was discontinued or the dosage decreased, 78% of patients had improved glycemic control. Hyperglycemia recurred in 8 of 10 cases with rechallenge. Conclusions. Number of reports, temporal relationship to start of olanzapine therapy, relatively young age, and improvement on drug withdrawal suggest that olanzapine may precipitate or unmask diabetes in susceptible patients.