Minced von Ebner's glands of rat tongue were incubated in vitro with histamine and histamine receptor antagonists. At various time intervals, media and homogenates of the tissue were assayed for lingual lipase and amylase activity and percentage secretion calculated. Histamine elicited moderate secretion (≈10%) of lingual lipase and amylase. In contrast, pyrilamine, and H 1 receptor antagonist, elicited>60% secretion. There were statistically significant differences between the percentage secretion of lingual lipase and amylase for basal secretion, as well as for histmine-and pyrilamine-evoked secretion of lingual lipase and amylase for basal secretion, as well as for histamine-and pyrilamine-evoked secretion above basal. The H 2 receptor inhibitors, cimetidine and ranitidine, stimulated secretion of only amylase, but not lingual lipase. When combined with histamine, these antagonists partially inhibited only the secretion of histamine-evoked lingual lipase, but not amylase. The differences in percentage secretion between the two enzymes indicate that exocytosis may not be the only process involved in protein secretion. The anomalous effects of the H 1 and H 2 receptor antagonists necessitate a more detailed characterization of the receptors of von Ebner's glands.