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Infectious bovine keratoconjunctivitis (IBK) is one of the most economically important diseases in preweaned calves. This study examined the health records of 45,497 calves over a 20-yr period to determine environmental and genetic factors influencing the incidence of IBK. Three data sets were analyzed with an animal model. The first data set (n = 41,986) evaluated environmental factors and genetic differences among nine purebred (Angus, Braunvieh, Charolais, Gelbvieh, Hereford, Limousin, Pinzgauer, Red Poll, and Simmental) and three composite breeds (MARC I, MARC II, and MARC III). Weaning weights of calves diagnosed with IBK were 8.9 kg lighter (P < 0.05) than weights of healthy calves. Incidence of IBK was related to age of the calf and the seasonal life cycle of the face fly (Musca autumnalis). Incidence of IBK increased in the spring (June), peaked during the summer months (July to September), and then decreased in the fall. Herefords were the most susceptible breed (P < 0.05) compared with all other purebreds and composites. Estimates of direct heritability for the incidence of IBK were generally low and ranged from 0.00 to 0.28 by breed. The maternal permanent environmental and genetic effects of the dam on the incidence of IBK were not significant for most breeds. The second data set (n = 9,606) was used to estimate heterosis for the incidence of IBK from a Hereford and Angus diallel design. The heterosis effect for the incidence of IBK in reciprocal Hereford/Angus crossbred calves was slightly negative (P = 0.12) but not large. The higher incidence of IBK in Angus × Hereford calves compared with Hereford × Angus calves (13.3 vs. 8.9%) suggests a maternal effect related to the incidence of IBK. Incidence of IBK in crossbred calves sired by tropically adapted breeds (Brahma, Boran, Tuli) compared with purebred and crossbred Bos taurus types was investigated in the third data set (n = 2,622). Crossbred calves sired by tropically adapted breeds had a lower incidence of IBK than most Bos taurus types (P < 0.05), but they were not different than either reciprocal crosses of Hereford and Angus or purebred Angus calves. Response to selection for decreasing the incidence of IBK is likely to be slow because of low heritability and low incidence in most breeds. Significant breed differences for incidence of IBK may be important to some producers and management systems.