We have investigated the responsiveness of adult guinea pig Schwann cells to a range of neuroligands, using ratiometric calcium imaging. The majority of cells responded to ATP (90 +/- 4%), adrenaline (57 +/- 5%), and noradrenaline (61 +/- 5%), as well as glutamate (60 +/- 5%). The number of cells responding to glutamate increased significantly (90 +/- 4%; p < 0.01) when the cells were grown in excitatory amino acid (EAA) free medium, indicating EAA-induced downregulation. Only a small number of cells (9 +/- 2%) responded to acetylcholine. Agonist and antagonist experiments show that these adult Schwann cells predominantly express ionotropic glutaminergic receptors (N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isooxazolepropionic acid (AMPA), and kainate) as well as alpha1-, alpha2-, and beta-adrenoreceptors. We conclude that Schwann cells derived from adult guinea pigs express a variety of neuroligand receptors when established in culture and are particularly rich in glutamate receptors. This probably reflects a de-differentiated state important to development and regeneration.