Our objective was to determine using electron microscopy how nonagouti (a), lethal yellow (Ar), and albino (c2J) genes affect the program of mouse hairbulb melanosome differentiation; 1,921 hairbulb melanosomes from four genotypes (a/a C/C = B,Ay/a C/C = Y, a/a c2J/c2J= BA, and Ay/a c2J/c2J= YA) were scored for developmental stage, length, and width.Qualitative and quantitative electron microscopy revealed the following. An albino locus‐induced diminution of melanosome size suggests that the albino locus is involved in structural features of melanosomes not directly related to the synthesis and deployment of tyrosinase. Ratio data on melanosome length‐to‐width confirm that the agouti locus determines melanosome shape, either spherical or elliptical; melanization is not required for melanosomes to achieve their agouti‐locus‐determined shapes. YA (Ay/a c2J/c2J) melanosomes, characterized by poorly organized matrices, absence of active tyrosinase, unusually large membrane invaginations, and significantly smaller dimensions than those of BA (a/a c2J/c2J), showed additive effects of both Ayandc2Jalleles.These data suggest that the albino locus plays a structural as well as functional (tyrosinase) role in the differentiation of mouse hairbulb melanosomes. The agouti locus, even in the absence of melanization, directs melanosome shape either via synthesis and deployment of agouti‐locus‐encoded matrix proteins or by other structural factors. The additive effects of Ayand c2Jalleles in compound YA mutants document the importance of specific interactions both functional and structural between agouti an