The toxicity of gossypol was studied in 20, 8-week-old feeder lambs that weighed approximately 16 kg. The lambs were allotted to 4 groups (A, B, C, D) and given (orally for 30 days) a daily dosage of gossypol (0, 45, 136, or 409 mg, respectively). Lambs were observed twice daily until they died or were euthanatized on the day the last dose was given. Clinical, electrocardiographic, clinicopathologic, pathologic, and toxicologic findings were recorded. All lambs given 409 mg of gossypol (group D) died before the end of the 30-day study. In this group, clinical signs included sudden death and/or chronic dyspnea syndromes. One group-B lamb had chronic dyspnea, but did not die. Electrocardiographic abnormalities observed in gossypol-treated lambs included increased amplitude of the T wave and decreased duration of the ST segment. Clinicopathologic alterations in group-D lambs included high serum total lactate dehydrogenase and lactate dehydrogenase liver-specific isoenzyme activities. Serum total creatine kinase activity decreased markedly in lambs of all groups treated with gossypol. Hemoglobinuria was detected in 2 group-D lambs. The average daily weight gain was remarkably consistent in lambs of all groups, except in 1 lamb each of groups D and B. Lambs were necropsied when they died or on day 30 of the study. The heart of gossypol-treated lambs weighted more than did that of untreated (control group A) lambs.(ABSTRACT TRUNCATED AT 250 WORDS)