An experimental mammary carcinoma was induced in Sprague-Dawley rats by the ip administration of N-nitroso-N-methylurea (NMU) in three doses of 50 mg/kg. In order to study the expression of histamine receptors in these experimental tumors, the presence of specific binding sites for histamine was studied. Using [3H]-histamine as a radioligand, two specific binding sites were characterized on the cell membrane. The first site, of high affinity, Kd = 4 +/- 2 nM, was further characterized as an H2 type using [3H]-cimetidine and [3H]-tiotidine as radioligands and by displacement experiments with different histamine agonists and antagonists. The second one of low affinity, Kd = 35 +/- 14 nM, needs further characterization. The determination of cAMP levels showed that histamine and the H2 agonist dimaprit, produced a significant decrease in the nucleotide concentration 6 minutes after stimulation, in a response that was specifically abolished by H2 antagonists. Based on these results, we conclude that neoplastic cells from NMU induced tumors express H2 histamine membrane receptors which are coupled to a transductional pathway different from cAMP production, which may be involved in the regulation of tumor growth.