The insecticide synergist piperonyl butoxide--alpha-[2-(2-butoxyethoxy)ethoxy]-4,5-methylenedioxy-2-propyltoluene--was tested for carcinogenicity in inbred F344 rats in a 2-year study employing doses of 10,000 and 5,000 ppm of the compound administered continuously in the feed. Although a statistically significant dose-related increase in the incidence of lymphoreticular neoplasia was associated with administration of the compound to females, the incidence of that class of neoplasm was higher in control males than in treated males. The finding of statistical significance in one sex is not considered by itself to constitute sufficient evidence of a biologic effect to justify an indictment of carcinogenic action. However, inasmuch as the chief use of this substance is to alter the in vivo metabolism of other chemicals, its possible role as a cocarcinogen should be carefully considered in any risk-benefit evaluation aimed at setting policies regarding its uses.