Changes in LAK susceptibility of tumor cells in which MHC class I antigen expression was undergoing regeneration following treatment at pH 3.0, were studied. P815 (murine mastocytoma) and RAJI (human B-cell leukemia) cell lines were briefly exposed to pH 3.0 buffer which brought down the MHC class I expression on these cells by 70-80% and resulted in a 3-fold increase in their susceptibility to murine and human LAK cells, respectively. During the MHC class I regeneration phase, LAK susceptibility fell and reached normal levels at a time point when MHC class I antigens had regenerated to a level which was 60-70% of the normal. Highly significant inverse correlations were obtained between LAK susceptibility and the log of MHC class I antigen expression, for both P815 and RAJI cell lines. These results indicate that during the MHC class I regeneration phase, there is an inverse correlation between MHC class I antigen levels and LAK susceptibility. Moreover, these results also suggest that the extent of change in LAK susceptibility may depend upon the levels of basal MHC class I expression on the tumor cells.