The complex enzyme phenol oxidase plays a major role in sclerotization and melanization of cuticle in insects. Production of active enzyme from the inactive proenzyme involves at least six protein components in Drosophila. We examine here the biochemical phenotype of two loci that affect phenol oxidase activity--quicksilver (qs; 1-39.5) and tyrosinase-1 (tyr-1; 2-54.5). Three mutations isolated by different procedures in three different laboratories are alleles at the quicksilver locus. The effects of these mutations have been monitored by means of enzyme assays in vitro and in polyacrylamide gels and by measurement of catecholamine pool sizes. The activity of all three active enzyme components (A1, A2, and A3) is reduced in qs mutants. The activated enzyme of one qs allele is thermolabile, while its activator is normal. Deletion and genetic mapping place tyr-1 near purple (pr; 2-54.5). Enzyme activity is reduced to 10% of normal but is not thermolabile and the activator is normal. The activity of all three A components is reduced. The diphenol oxidase activity in double mutant combinations shows that these mutations and Dox-A2 (Pentz et al., 1986) affect this enzyme in different ways.