The long-acting sulfonamide antibacterial, sulfadimethoxine, has the potential for use in pen-held lobsters, Homarus americanus for treatment of gaffkemia. We evaluated the disposition of sulfadimethoxine after intrapericardial, oral or multiple oral administration of unlabelled or radiolabelled sulfadimethoxine (42 mg/kg) to 500 g lobsters. Elimination of parent sulfadimethoxine from hemolymph was very slow compared with elimination of the drug from blood of vertebrate species; the beta phase half-life was 77 hr in lobster as opposed to 7-40 hr in several vertebrate species. The pharmacokinetics of sulfadimethoxine after intrapericardial administration were linear up to 55 mg/kg, and binding of sulfadimethoxine to hemolymph proteins was constant over the range 14-200 micrograms/ml. During the first week after dosing, concentrations of sulfadimethoxine and metabolites (total radioactivity) were similar in all non-excretory tissues, such that muscle, shell and hemolymph contained the largest percentage of the administered dose. By 2 weeks and later, hepatopancreas and digestive tract contained the highest concentration and percentage of the dose, by total radioactivity. Part of the dose of sulfadimethoxine was excreted unchanged in urine and part was metabolized in hepatopancreas to unknown polar metabolites. The major vertebrate metabolite, N-acetylsulfadimethoxine, was a very minor metabolite in lobster. Although sulfadimethoxine was extensively metabolized in hepatopancreas, the polar metabolites were very slowly excreted, suggesting inefficient excretion mechanisms for elimination of polar xenobiotic metabolites in the lobster.