The role of insulin resistance in the tumor-induced decrease in tissue lipoprotein lipase (LPL) activity was studied in vivo and vitro in methylcholanthrene-induced sarcoma-bearing rats. Intraperitoneal (i.p.) injection of 2U of regular insulin resulted in high-adipose LPL activity in control rats (CTR) of 122.0 +/- 42.4 U/mg tissue, but it had little effect on tumor-bearing rats (TBR), which showed a value of only 9.6 +/- 5.5 U/mg tissue (P = 0.002). When adjusted for serum insulin concentrations, adipose LPL activity remained significantly different between the TBR and CTR at 0.19 +/- 0.17 and 0.78 +/- 0.29 U/mg tissue, respectively (P = 0.02). Following the in vitro incubation with either 1.44 g/l glucose of 1 x 10-8 U insulin of adipose tissue fragments obtained from the TBR and the CTR, measurable LPL activity was maintained in the tissue from the CTR for 2 h but not in that from the TBR. These results suggest that the decreased LPL activities seen in the tumor-bearing state may be mediated by insulin resistance.