An adult male grey seal (Halichoerus grypus), treated successfully a month earlier for a cutaneous aspergilloma, suddenly developed depression, lethargy and severe expiratory dyspnea and was examined. The animal had severe congestion and consolidation of both lungs but had normal total and differential leukocyte counts, erythrocyte parameters and routine serum chemistries. Because of his previous history he was again placed on systemic ketaconazole therapy. The animal initially appeared to improve. Subsequent results of agar plate immunodiffusion tests for antibody to histoplasmosis, blastomycosis and aspergillus using human positive serum controls were negative. Routine skin tuberculin tests of aquarium employees revealed positive conversions in two of the three mammalogists caring for the seals. The third mammalogist had erythema but no induration. This lead to evaluation of the seal's banked serum with an ELISA using Mycobacterium bovis antigen and conspecific controls. The symptomatic seal was positive with increasing titer. Serum samples from one other grey seal and five harbor seals in the same enclosure were tested, and only the other grey seal had titer. Banked serum samples indicated this seal had high titers on arrival at the aquarium three years previous and these titers had not fallen. Comparative skin testing using intradermal injections human PPD, bovis PPD, and avium PPD in the webbing of the rear flippers resulted in erythema and induration in all seals in the exhibit. Mycobacterium fortuitum was cultured from nasal swabs from 3 seals, including the male grey seal. All seals were placed on 5 mg/kg daily oral isoniazid therapy and 25 mg supplemental pyridoxine. The grey seals were additionally placed on daily oral rifampin (10 mg/kg). The clinically affected male grey seal improved and became asymptomatic, but later developed nervous tremors and Muscle spasms. These subsided with temporary cessation of therapy followed by a 50% reduction in isoniazid dose. Later the female grey seal also developed less prominent subcuticular Muscle fasciculations which also responded to temporary suspension of therapy and subsequent reduced dose.