To determine if murine lymphocytes activated by interleukin 2 (IL-2) were cytotoxic against syngeneic elicited peritoneal macrophages (M phi) infected with intracellular pathogens, splenocytes that had been cultured with IL-2 for 5 or 10 days were studied in vitro. These cells, [lymphokine-activated killer (LAK) cells] showed significantly greater cytotoxicity against M phi infected with Leishmania major or Legionella pneumophila than against uninfected M phi. Preferential cytotoxicity against infected M phi was best shown using effector-to-target-cell ratios of 1:1-20:1; when ratios greater than or equal to 40:1 were employed, uninfected M phi were also lysed. The extent to which M phi that had been incubated with L. major were lysed depended upon the proportion of M phi containing intracellular organisms. After infection with L. major, the duration of incubation did not appear to influence the degree of lysis by LAK cells.