We evaluated the potential for gossypol intoxication and resulting effects of feeding large amounts of cottonseed meal to dairy cows in early lactation. Twenty-four Holstein cows were grouped by age, prior production, and days postpartum and randomly assigned to one of three diets. After 14-day standardization cows individually were fed a blended corn-corn silage ration supplemented with screw-pressed cottonseed meal, direct solvent extracted cottonseed meal, or soybean meal during a 14-wk comparison. Packed cell volume, copper in plasma, activities of transaminases, and gross composition of milk were not affected by ration. Hemoglobin was depressed, and total protein of plasma was elevated by the 9th wk in cows fed the solvent meal. Erythrocyte fragility was detected in those cows by the 7th wk and appeared later in cows fed the pressed meal. Gossypol was identified and quantitated in plasma and liver but was not detected in erythrocytes or milk from cows fed cottonseed meal. Elevated ambient temperatures precipitated increased respiration rates in the cows fed solvent meal. Physiological changes and gossypol in tissues of cows suggest that intoxication is possible in mature ruminants consuming cottonseed meal containing high free gossypol.