Despite histamine being a potent endogenous vasoactive agent released in increasing amounts postburn, its role in postburn oedema formation has been controversial and its effect on burn circulation poorly investigated. The present study investigated the involvement of H(1), H(2) and H(3) receptors in postburn edema in rats exposed to skin and muscle burns and their influence on skin circulation postburn. We used the selective antagonists clemastine (H(1)), ranitidine (H(2)), thioperamide (H(3)) and the selective H(3) receptor agonist, imetit. Results showed that none of the antagonists or the H(3) agonist had significant effect on postburn edema measured by quantitative spectrophotometric analysis of extravasated Evans blue-albumin in the full-thickness burned skin or muscle. Clemastine and thioperamide failed to induce significant effect on blood flow in the partial- or full-thickness skin burn injury as measured by laser Doppler flowmetry, while ranitidine significantly (P<0.01) reduced blood flow in the full-thickness burn. In contrast, the H(3) receptor agonist, imetit, significantly increased blood flow, both in the partial-thickness burn injury (P<0.05) and in the full-thickness burn (P<0.01). Moreover, imetit significantly (P<0.01) increased mean arterial pressure while thioperamide significantly (P<0.01) reduced systemic pressure. In conclusion, H(1), H(2) and H(3) receptors are not important actors in the regulation of vascular patency permeability, whereas H(3) receptors play an important role by increasing skin circulation postburn, presumably by relaxation of vascular smooth muscle and/or by interacting with other inflammatory neurotransmitters. Data also suggest that H(2) receptor blockers may not be best choice for stress ulcer prophylaxis in burn patients.