We describe the use of recombinant Semliki Forest virus (SFV) vectors for efficient expression of the rat histamine H 2 (rH 2 ) receptor in COS-7 (African green monkey kidney cells) cells. Recombinant SFV-infected COS-7 cells express the histamine rH 2 receptor in a time-dependent fashion with a maximum expression level of 50 pmol mg - 1 after 40 h. SFV-mediated histamine rH 2 receptor expression shows similar pharmacological properties as the receptor expressed transiently or stably in mammalian cells. In addition, we demonstrate the pharmacological and functional characterisation of the D 1 1 5 N mutated histamine rH 2 receptor. It has been shown that the D 1 1 5 N mutation renders the receptor constitutively active and structurally unstable. The rapid onset of and high maximal expression levels obtained from SFV-infected COS-7 cells enabled us to characterise this mutant receptor. We prove that recombinant SFV vectors are powerful tools for heterologous expression of G-protein-coupled receptors and that one can achieve both the high-level gene expression described for baculovirus-infected insect cells and the use of mammalian cells as hosts.