AbstractAn extensive review of the literature revealed that orally administered thalidomide produces a variable teratogenic response in rabbits at equal doses; while rats are uniformly resistant to the teratogenic effects of thalidomide. In an effort to explain these individual and species differences a study was made comparing the oral absorption of 3H‐thalidomide suspension in these species under identical conditions at teratogenic dosage levels (50, 100, and 200 mg/kg). New Zealand white female virgin rabbits and Sprague‐Dawley female virgin rats were employed. Unlike rats, rabbits were quite variable in absorbing thalidomide suspensions, and this was presumably related to the delayed gastric emptying time in some animals. However, the mean plasma concentrations were similar in both species during multiple daily administration of thalidomide suspensions. When thalidomide was administered to rabbits in hard gelatin capsules it was poorly absorbed because of slow dissolution of the powdered drug in gastrointestinal fluids. Regardless of the dosage form administered, only negligible absorption occurred from the rabbit stomach. The small intestine was shown to be the site of absorption in rabbits. These results suggest that the absorption of orally administered thalidomide suspension is so similar in rabbits and rats that it could not be responsible for the species difference in its teratogenic potency. However, the availability of thalidomide from encapsulated powder is so poor in rabbits that the positive teratogenic results recorded in the literature with this dosage form are questionable.