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HL60 is a human promyeloid cell line capable of differentiating towards monocytes or granulocytes when treated with appropriate agents. Changes in insulin receptor number, affinity and mRNA levels were observed when HL60 cells were induced to differentiate with 12-O-tetradecanoyl-phorbol-13-acetate (TPA) or dimethylsulphoxide (DMSO). Total and high-affinity insulin receptor numbers decreased following treatment of HL60 cells with DMSO, whereas total insulin receptor number increased and high-affinity receptor number decreased in cells treated with TPA. Three distinct insulin receptor mRNA species of 9·1, 6·3 and 2·8 kb were identified in HL60 cells. The larger 9·1 and 6·3 kb species were increased in both TPA- and DMSO-treated HL60 cells, and the 2·8 kb mRNA was reduced in differentiated cells. Thus HL60 cells differentiated towards monocytes or granulocytes showed similar changes in the levels of individual insulin receptor mRNAs, but displayed contrasting alterations in low-affinity insulin binding. Three HL60 variant lines, which have different capacities to respond to inducers of monocyte and neutrophil differentiation, showed similar levels of total insulin receptors, but differed in their expression of high-affinity receptors. The data provide evidence for the existence of two distinct insulin receptors.