Permethrin resistance in the Learn-PyR strain of house fly was examined in four genetically derived substrains, each being homozygous for a different "resistant" autosome of the Learn-PyR strain. The resistance of these derivative strains was characterized toxicologically and biochemically. The relative levels of resistance to permethrin conferred by each autosome were 5 greater than 3 greater than 1 greater than 2. Three factors were associated with resistance: (1) increased mixed-function oxidase (MFO) activity associated with elevated levels of cytochrome P-450, cytochrome b5, and NADPH-cytochrome c reductase (P-450 reductase) activity; (2) target-site insensitivity (kdr); and (3) decreased cuticular penetration. Permethrin resistance factors on chromosome 1 consisted of a piperonyl butoxide (PB)-suppressible mechanism correlated with increased levels of cytochromes P-450 and b5; on chromosome 2, a PB-suppressible mechanism associated with elevated amounts of cytochrome P-450; on chromosome 3, decreased cuticular penetration, kdr, and increased amounts of P-450 reductase activity; and on chromosome 5, a largely PB-suppressible mechanism correlated with elevated levels of cytochrome P-450 and P-450 reductase activity.