Drug interactions with technetium Tc-99m gluceptate resulting in altered biodistribution were studied using chart review and animal tests. Charts of nine patients who had abnormal gallbladder uptake of technetium Tc-99m gluceptate during a two-year period were reviewed to obtain data such as concurrent drug therapy, primary diagnosis, and laboratory values. Adult New Zealand white rabbits were then used for testing the biodistribution of technetium Tc-99m gluceptate when administered concurrently with possibly interacting drugs identified in the chart review--penicillamine, penicillin G potassium, penicillin V potassium, acetaminophen, and trimethoprim-sulfamethoxazole. Chart review revealed no conclusive patterns of altered biodistribution associated with other factors. The data did suggest the possibility that the five drugs listed above might cause increased hepatobiliary clearance of the radiopharmaceutical. Animal tests showed that i.v. penicillamine caused substantial distribution of radioactivity into the gallbladder and small bowel. Minimally increased gallbladder radioactivity occurred when oral acetaminophen and trimethoprim-sulfamethoxazole were administered concurrently. Oral and i.v. penicillins did not increase gallbladder activity. Penicillamine may cause substantial alteration of the biodistribution of technetium Tc-99m gluceptate.