Between May and December 1984, an epizootic of leptospirosis in California sea lions (Zalophus californianus) occurred along the west coast of the United States from Monterey County, Calif, northward to Seattle, Wash. Clinical signs observed were severe depression, excessive thirst, and tucked-up posturing, with associated leukocytosis and increased globulin, BUN, and creatinine values. Effective antibiotic therapy consisted of tetracycline (22 mg/kg of body weight every 8 hours, orally) or potassium penicillin G (44,000 U/kg every 12 hours, orally or IM) for 10 to 14 days. Sixty-six sea lions were treated successfully and released. Necropsies of animals that died indicated marked kidney swelling, darkened reniculi, and poorly differentiated cortices and medullae, thick, black bile in gallbladders, thick, pale yellow pericardial fluid, and friable hemorrhagic mesentery. Primary histologic lesions were tubular nephritis and glomerulonephritis. Darkfield microscopy of kidney macerates and/or urine, and results of the microscopic agglutination test, using Leptospira serovar pomona-killed antigen led to a presumptive diagnosis of leptospirosis. Bacteriologic isolation and identification is ongoing. The epizootic primarily affected juvenile or subadult male California sea lions migrating northward from breeding rookeries of southern California's Channel Islands.