The treatment of cells with soluble glycoproteins or UVinactivated virus has provided strong evidence that HSV-1 binding to the plasma membrane triggers signal transduction in the host cell as a prelude to infection, but interpretation of these experiments is not straightforward. The use of soluble glycoproteins does not mimic the binding of individual virus particles and the physiological significance of the results is difficult to assess. The use of UV-inactivated particles in signalling studies simulates infection but these particles are able to enter cells and deliver virion proteins to the cytoplasm. Experiments with UV-inactivated particles do not therefore distinguish between events arising from virus binding from those resulting from virus entry.