Methylglyoxal (2-oxopropanal) is the physiological substrate of the glyoxalase system. When exogenous methylglyoxal (50 microM-1 mM) was added to human leukaemia 60 (HL60) cells in culture (5 x 10(4) cells/ml), inhibition of growth and toxicity was induced. The median growth inhibitory concentration IC50 value was 238 +/- 2 microM. There was little differentiation of HL60 cells induced by methylglyoxal (a maximum of 2% differentiation with 500 microM methylglyoxal). There was no similar toxicity induced by methylglyoxal in corresponding differentiated cells, neutrophils, under the same culture conditions. Cell growth and toxicity induced by methylglyoxal (250 microM) in HL60 cells occurred in the initial 24 h of culture, after which residual surviving cells exhibited normal growth kinetics. It could also be prevented by replacing the culture medium in the initial 6 h of culture; thereafter, irreversible toxicity developed, reaching the maximum value after 24 h of culture. Growth arrest and toxicity induced by methylglyoxal increased with increasing serum composition of the medium. The mechanism of toxicity is unknown.