Early dietary exposure to cow's milk proteins has been proposed as an important environmental factor in the development of IDDM both in humans and in diabetes-prone rodents. To examine the significance of cow's milk protein in IDDM, 120 NOD mice were maintained, starting from conception until sacrifice, on one of four diets: standard PMI Picolab Rodent Diet 20, a milk- free modification of the standard Picolab diet, a milk-free diet incorporating 0.036% bovine serum albumin (BSA), and a milk-free diet including 0.036% bovine IgG (BGG). The cumulative IDDM incidence at 7 months for these mice in a specific pathogen-free environment on the respective diets was 78, 93, 93, and 67% for females, and 17, 54, 17, and 0% for males. The ages of diabetes onset and insulitis scores were similar for mice on each diet. The unexpectedly lower incidence of IDDM in mice on the milk-free diet that included BGG raises the possibility this cow's milk protein might possibly have some protective effect against the development of IDDM in NOD mice. Our main finding was that the standard, milk-free, and BSA-containing diets resulted in comparable incidences of IDDM in NOD mice, demonstrating that neither cow's milk whey proteins in general nor BSA in particular are significantly important as etiologic dietary agents in IDDM in NOD mice.