SummaryOculocutaneous albinism type 1 (OCA1) is an autosomal recessive disorder caused by mutations in the tyrosinase gene. Two subtypes ofOCA1 have been described: severeOCA1A with complete absence of tyrosinase activity and less severeOCA1B with residual tyrosinase activity. Here, we characterize the recombinant human tyrosinase intramelanosomal domain and mutant variants, which mimic genetic changes in both subtypes ofOCA1 patients. Proteins were prepared using site‐directed mutagenesis, expressed in insect larvae, purified by chromatography, and characterized by enzymatic activities, tryptophan fluorescence, and Gibbs free energy changes. TheOCA1A mutants showed very low protein expression and protein yield and are enzymatically inactive. Mutants mimickingOCA1B were biochemically similar to the wild type, but exhibited lower specific activities and protein stabilities. The results are consistent with clinical data, which indicates thatOCA1A mutations inactivate tyrosinase and result in severe phenotype, whileOCA1B mutations partially inactivate tyrosinase and result inOCA1B albinism.