Histamine is present in the central nervous system and is believed to be derived from neurons (50 percent) and mast cells (50 percent). This experiment was designed to analyze histologically the numbers and distribution of brain-associated mast cells in normal (+/+), mast cell deficient (W/W^v) and heterozygote (W/+, W^v/+) mice of the WBB6F_1 /J strain. Significant variations in the number and distribution of mast cells between the various genotypes were found. Based on the results, a hypothesis is proposed to account for the observed genotypical differences in mast cell numbers and distribution. Based on the total number of mast cells and the content of histamine in a typical mast cell, it is apparent that the mast cell is not a major source of brain histamine, suggesting that another non-neuronal pool of histamine must be present in the brain.