A comparison was made of the capacity of bone marrow cells (BM) from genetically distinct strains of mice to develop into mast cells under defined conditions of in vitro culture. In the presence of conditioned media derived from ConA treated spleen cells from normal or Trichinella spiralis-infected mice, mast cell development occurred readily. After 21 days of culture mast cells comprised more than 90% of the total cell population. BM taken from certain strains of mice (SWR and NIH) produced large numbers of mast cells, total cell numbers increasing between 2 and 5 fold; other strains (C57BL/10 [B10] B10 congenics) produced relatively few mast cells, total cell numbers not increasing above the starting concentration or declining during culture. The genetic factors determining the strain-response phenotype (no. of mast cells in culture) were predominantly associated with the background genome. No significant differences in response were noted between the B10 congenic strains B10 [H-2b], B10.G [H-2q] or B10.BR [H-2k], which differ only at the MHC, whereas major differences were seen between B10.G and the other H-2q strains [SWR and NIH]. Response phenotype was not inherited as a simple dominant trait; F1 progeny of high x low responder strains were intermediate between the parental values. The expression of genetic influences upon mast cell response phenotype appears to be at both the level of mast cell precursor cells, as determined from limiting dilution assays of BM from high, low and F1 (high x low) strains, and at the level of mast cell proliferation, as determined by repeated sub-culture of mast cells from these strains.