Between January 1990 and August 1995, 382 harbor seal pups (Phoca vitulina richardsii) that stranded live along the central and northern California coast died during rehabilitation at The Marine Mammal Center, Sausalito, California. 162 of these were examined histopathologically. In 33% (54/162) of these, intranuclear inclusion bodies suggestive of herpesvirus infection were observed in adrenal cortical cells and hepatocytes. Affected animals died between 0 and 62 days following admission to the Center. The majority of cases occurred between mid-April and mid-May in each year. Prevalence of inclusion bodies did not differ between the sexes (29/96 males, 25/66 females), but was greatest in pups that stranded in Monterey county (24/33, 73%) and lowest in pups that stranded in Humboldt county (1/13, 7.7%). Clinical signs of infection varied from chronic weight loss to sudden death. On post mortem examination, 19 of the 54 affected pups showed no gross lesions other than adrenocortical atrophy. Histologic examination revealed acute multifocal adrenocortical and hepatic necrosis, with amphophilic, smudgy intranuclear inclusions typical of herpesvirus infections. Syncytia were sometimes present in the adrenals but not in the liver. The other 35 pups had a variety of lesions including, in decreasing order of frequency: omphalitis, suppurative bronchopneumonia, meningitis, enterocolitis, cutaneous abscesses and septic arthritis. These animals had similar inclusions in adrenal cortical cells and hepatocytes. Transmission electron microscopic examination of adrenal glands with inclusion bodies revealed icosahedral viral particles, about 100 nm in diameter, both with and without outer envelopes. Primary adrenal cell cultures were established from harbor seals, and inoculated with adrenal gland homogenate from animals with inclusion bodies. Cytopathic effect (cell rounding and plaque formation) was observed in the primary cell lines, but could not be transmitted to Vero cell lines. These data suggest a herpesvirus is prevalent in wild harbor seal populations in central California. Herpesviruses typically display latency and persistence of infection, with reactivation of infection occurring as a consequence of a variety of immunosuppressive events. It is likely that the virus infecting these harbor seals possesses these properties, reactivation of infection potentially resulting from events such as maternal separation, over-crowding, disturbance by man or his pets, or infection with bacterial pathogens.