If cultured over 10 days, peritoneal cells from different strains-CBA/J, C3H, C57B1, DBA/2, Balb/C, NZB and congenitally athymic Nude (Nu+/Nu+), fifth backcross generation with Balb/C-of unimmunized mice developed high numbers of plaque-forming cells against sheep erythrocytes (up to 13 per cent of the recovered viable cells at day 6) without being triggered by antigen. Plaque-forming cells could be demonstrated by all methods of local hemolysis (agarose, liquid medium, CMC). This capacity increase with the age of the donor mice. The phenomenon is immunological, as plaque formation could be inhibited by specific anti-mouse IgM serum and is complement-dependent. It also displays immunological specificity: the erythrocytes from sheep, goat, cow, which cross react when tested in the classical mouse immune spleen cells system, give hemolysis plaques with cultured mouse peritoneal cells, while horse, rabbit rat erythrocytes, non cross reacting with sheep erythrocytes in the classical immune systems, give no plaques with peritoneal cells. The removal of cells adherent to glass does not diminish the ability of the peritoneal cell population to form plaques against sheep erythrocytes. These results suggest that peritoneal lymphocytes constitute a highly specialized population of already programmed cells which become derepressed when removed from their natural environment and exposed to cell-culture conditions.