[3H]Inositol phosphate responses to histamine and a range of other agonists were studied in cultured human tracheal smooth muscle cells. Histamine (EC50 6.5 microM), bradykinin (EC50 9.7 nM), carbachol (EC50 10 microM), substance P and NaF all produced concentration dependent [3H]inositol phosphate formation in these cells. The response to histamine was inhibited by mepyramine (KA 4.3 x 10(9) M-1), indicating the involvement of the histamine H1 receptor in this response. The inositol phosphate response to histamine was apparently desensitized following prolonged agonist exposure. The response to histamine was inhibited by phorbol dibutyrate (IC50 6 nM), and this inhibitory effect was reversed by staurosporine (150 nM). Isoprenaline (1 microM), rolipram (0.1-100 microM) and 3-isobutyl-1-methylxanthine (0.1 mM) all produced small inhibitory effects upon histamine induced inositol phosphate formation. These results demonstrate that cultured human tracheal smooth muscle cells express histamine H1 receptors coupled to phosphoinositidase C and suggest that the inositol phosphate response induced by stimulation of this receptor subtype is inhibited by activation of protein kinase C and, to a lesser extent, by elevation of cell cyclic AMP content.