A plasmacytoid leukemia of chinook salmon, Oncorhynchus tshawytscha, has recently been recognized in seawater netpens in British Columbia, Canada. The disease has occurred at several sites and has caused high mortality. Plasmacytoid leukemia is characterized by a generalized invasion of visceral tissues and the orbit of the eye by plasmacytoid cells. The disease was experimentally transmitted to healthy chinook salmon by i.p. injection of kidney tissue homogenates, but transmission with a cell-free filtrate was equivocal. In another experiment, chinook salmon, coho salmon, O. kisutch, sockeye salmon, O. nerka, rainbow trout, O. mykiss (or Salmo gairdneri), and Atlantic salmon, Salmo salar, were given injections of a tissue homogenate from affected chinook salmon. Ten wk after exposure, plasmacytoid leukemia was observed in all of the sockeye salmon and chinook salmon, one of ten Atlantic salmon, and none of the rainbow trout. Seven of the ten coho salmon examined at 10 wk had lesions suggestive of early development or a mild form of the disease. Multifocal areas of proliferating cells resembling plasmablasts were observed in the visceral fat, and the kidneys exhibited mild to moderate hyperplasia of the hematopoietic interstitium. Our studies support the hypothesis of an infectious etiology for plasmacytoid leukemia, but the agent, perhaps an oncogenic virus, has yet to be detected.