The acute oral toxicity (LD₅₀) of equi-toxic doses of malathion plus a Carbamate insecticide was determined in mice and rats. The observed LD₅₀ of a “mixture” was compared with the expected LD₅₀ calculated from each LD₅₀ and LD₅₀ (expected)/LD₅₀ (observed) was used as a ratio of combined effect. Of 5 combinations studied in male mice, malathion plus BPMC was the only combination which exhibited a striking synergism (the ratio, 5.4). On the other hand, clear synergism was not observed with the combination of malathion plus one of the other carbamate insecticides, MTMC, NAC, XMC or MPMC. When malathion or BPMC was administered alone, the toxicity in female mice or male rats was not different significantly from that in male mice. In female mice, the synergism of malathion plus BPMC was similar to that in male mice (the ratio, 5.2). However, relatively less potent synergism was noted with the combination in male rats (the ratio, 2.0). The marked synergism of malathion plus BPMC could not be explained on the basis of an inhibition of the acetylcholinesterase (AChE) by malaoxon plus BPMC, or an inhibition of malathion's detoxication by BPMC.