Isolated guinea-pig lung parenchymal strips (GPLS) relaxed in response to the selective histamine H2-receptor agonists, dimaprit and 4-methylhistamine (4-MeH), and to low doses of histamine (10(-9) to 10(-7) mol/l) and contracted in response to several spasmogens. The order of the relative activity of the spasmogens was 2-methylhistamine (2-MeH) greater than histamine greater than carbachol greater than 2-pyridylethylamine (2-PE). Dimaprit and 4-MeH also relaxed GPLS which were contracted by 2-MeH, 2-PE or carbachol. Metiamide (a selective H2-antagonist: 5 x 10(-5) mol/l inhibited or reversed relaxations to histamine, dimaprit and 4-MeH, and significantly enhanced contractile responses to histamine without altering responses to carbachol. Mepyramine (a selective H1-receptor antagonist: 10(-8) to 10(-6) mol/l antagonized histamine-induced contractions. This investigation shows: (1) histamine is more active than carbachol in GPLS and (2) the occurrence of histamine H1-receptors mediating contraction and H2-receptors mediating relaxation in guinea-pig lung.