Histamine N-methyltransferase (HNMT) catalyzes the N tau-methylation of histamine and structurally-related compounds. Levels of HNMT activity in the human red blood cell are regulated by inheritance. The inbred mouse is an ideal laboratory animal in which to study the genetics of inherited traits. Therefore, HNMT activity was measured in renal homogenates of A/J mice to establish optimal assay conditions and to determine the properties of mouse kidney HNMT as a first step toward testing the hypothesis that large strain-related variations in HNMT activity might exist among inbred strains of mice. Apparent Km values for histamine and S-adenosyl-L-methionine, the two cosubstrates for the reaction, were 26 and 1.7 microM, respectively. IC50 values for the inhibition of mouse kidney HNMT by amodiaquine and S-adenosyl-L-homocysteine were 1.67 and 11.8 microM, respectively. HNMT activity levels were then measured under optimal assay conditions in renal preparations from male animals of eleven inbred mouse strains chosen because of the availability of recombinant inbred (RI) animals derived from the parental strains. Average values for renal HNMT activity varied among strains by less than two-fold and ranged only from 26.2 +/- 0.51 (mean +/- SEM) units/mg protein in AKR/J mice to 39.1 +/- 2.58 units/mg protein in C57BL/6J animals. Renal HNMT activities in females of the three strains in which both sexes were studied were 11-13% higher than were those in renal tissue from males of the same strain. In summary, the properties of HNMT in the mouse kidney are similar to those of HNMT in other species, but strain variation in levels of enzyme activity among the 11 inbred mouse strains studied was insufficient for these animals to be used in biochemical genetic experiments.