Fifteen calves of two sires were fed endophyte infected (E + ) fescue seed to quantify differences in susceptibility to fescue toxicosis among sire groups. One of the sires, a Polled Hereford, had a commercial reputation of producing calves with less severe symptoms of tall fescue toxicosis than their contemporaries. The control sire, also a Polled Hereford, had unknown merit with regard to offspring susceptibility to fescue toxicosis. The study was divided into five phases, two in which endophyte-infected fescue seed was included in the diet (phases two and four) and three in which fescue seed was not in the diet (phases one, three, and five). All calves were treated similarly and given the same opportunities for water, shade and socialization. Susceptibility to fescue toxicosis was measured by appetite (amount of feed consumed per day per unit of metabolic body weight), serum prolactin, cholesterol, and alkaline phosphatase concentrations, ability to maintain homeotherny (afternoon minus morning rectal temperature), ability to dissipate core body heat (afternoon minus morning surface temperature), and heat-transfer inefficiency (afternoon rectal minus afternoon surface temperatures). Appetite was decreased by the E + fescue seed, but the sire groups did not differ in their response to or recovery from E + fescue seed. The E + fescue seed caused prolactin to decrease (P < .0001) but the sire groups did not differ in their responses to addition or withdrawal of E + fescue seed from the diet. Cholesterol levels were lower overall (P < .001) when the E+ fescue seed was fed, and the sire groups recovered from the fescue toxicity at different rates (P < .001). Alkaline phosphatase concentrations were lower during the phases when E + fescue seed was fed; calves from the control sire were less resistant to the E + fescue seed effects than the Missouri calves (P < .0001). Ability to maintain homeothermy was reduced by the E + fescue seed, but the reduction did not differ between sire groups. Surface temperature changes and heat-transfer inefficiencies were not indicative of fescue toxicosis in this study. It was concluded that serum cholesterol and serum alkaline phosphatase concentrations may be accurate indicators of differences among paternal half sib groups of cattle in susceptibility to fescue toxicosis.