The toxicity of Prednisolone farnesylate (PNF) gel, a synthetic glucocorticoid, was investigated in the Beagle dog. PNF gel was administered percutaneously at doses of 0.2, 0.8 and 3.2 mg/kg/day for 13 weeks, then the drug was withdrawn for 5 weeks to evaluate the reversibility. In addition, 2 mg/kg/day prednisolone gel (PN gel), which is approximate to 3.2 mg/kg/day PNF gel in prednisolone molarity, was also administered for comparison. The results are summarized as follows: 1. No deaths were observed in any of the PNF gel test groups or the PN gel group, nor were there any abnormal findings in the clinical signs of the animals. 2. In the hematology, a tendency toward a decrease in the lymphocyte ratio was observed in males from the PNF gel 0.8 mg/kg/day and above groups. In the PN gel group, a significant decrease or a tendency toward a decrease in the lymphocyte ratio was observed, as well as an increase in the white blood cell count in some animals. 3. In the blood biochemistry, a significant decrease or a tendency toward a decrease in total cholesterol and phospholipid was observed in males from the PNF gel 3.2 mg/kg/day group and a tendency toward an increase in triglyceride in females from the PNF gel 3.2 mg/kg/day group was observed. In the PN gel group, a tendency toward an increase in AIP activity, a tendency toward an increase in triglyceride were observed. 4. In the histological examinations, a decrease in the weight of the thymus and adrenal glands, vacuolation of hepatocytes in the middle zone of the liver, atrophy of zona fasciculata of the adrenal glands, hypertrophy of zona glomeruli, swelling of cortical cells of zona faciculate and atrophy of the thymus were observed in the PNF gel 0.8 mg/kg/day and above groups. In the PN gel group, atrophy of submandibular lymph nodes and mesenteric lymph nodes was observed in addition to the same changes as observed in the PNF gel groups. Furthermore, thinning, atrophy or a decrease in the weight of the adrenal glands was also observed both in the PNF gel 3.2 mg/kg/day group and the PN gel group at the end of the 5-week recovery period. 5. As described above, a decrease in the lymphocyte ratio, in the weight of the thymus and adrenal glands and vacuolation of hepatocytes were observed in the PNF gel 0.8 mg/kg/day and above groups.(ABSTRACT TRUNCATED AT 400 WORDS)