Eight squirrel monkeys (Saimiri sciureus) challenged with EBV or EBV-transformed SLCL were naturally or experimentally infected with Plasmodium knowlesi or Pl. brasilianum. Most of the animals had been splenectomized and unilaterally nephrectomized. Three of these monkeys received one dose of 6 to 12 X 10(8) autologous SLCL. These lines were derived from saimiri lymphoid cells permanently transformed by B-EBV in vitro. All three animals developed multiple undifferentiated malignant lymphomas and died 8 to 10 days post inoculation. Necropsy tumor specimens were EBNA-positive and contained 7 to 21 EBV genome equivalents per cell. EBNA- and EA-positive SLCL were established in vitro from four tumor explants of two monkeys. These results demonstrate that in vitro EBV-transformed SLCL are able to cause tumor formation in autologous squirrel monkeys. Five monkeys received high transforming doses of B-EBV or S-EBV, derived from one of the tumorigenic SLCL. None of the animals developed any sign of tumor formation during an observation period of up to 130 days. Three of these monkeys showed no detectable EBV-related seroconversion while the sera of two monkeys had become anti-EBNA-positive when tested at days 28 and 130 respectively post inoculation. Two additional monkeys received neither EBV nor SLCL. They showed no clinical evidence of tumor development or spontaneous seroconversion over a period of more than 1 year.