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A system is described for the study of the in vitro synthesis of bovine keratohyalin for periods of up to 24 h. Keratohyalin granules appeared morphologically unaltered during culture, although histochemical stains for RNA indicate a markedly diminished RNA content by 6 h. Incorporation of tritiated histidine began slowly, then became linear between 4 and 24 h in serum-containing media. However, following pre-incubation in serum-free media, increased incorporation occurred from time zero. The internal variation of the system using a standard 6 h pulse was +/- 10, +/- 24, +/- 22, +/- 18% in four separate experiments. Measurements of modulations in bovine keratolhyalin synthesis in vitro may prove useful in the development of drugs of therapeutic potential in dermatology.