We examined the relationship between cellular glutathione (GSH) level and susceptibility to lymphokine-activated killer (LAK) cell-mediated cytolysis in KB human pharyngeal carcinoma cells. Treatment of KB cells with D,L-buthionine-S,R-sulfoximine (BSO), a gamma-glutamyl cysteine synthetase blocker, resulted in decreased total intracellular GSH levels associated with increased susceptibility to LAK killing. In contrast, treatment with oxothiazolidine-4-carboxylate (OTZ, a precursor of cysteine), which is known to increase cellular GSH level, decreased the susceptibility of KB cells to LAK killing. Both agents had no effects on binding frequency of KB cells to LAK cells. These results suggest that intracellular GSH in tumor cells play a protective role against LAK mediated cytolysis, specially in the post-binding killing phase.