Prostaglandin synthesis by astrocytes in culture has been shown to be stimulated by a range of mediators including ATP, interleukin-1 and the neuropeptide substance P. In this paper we present evidence that astrocytes from rat spinal cord, but not other CNS regions, release prostaglandins in response to treatment with sub-micromolar concentrations of the neuropeptide substance P, a neuromodulator that may be involved in regulating the input of nociceptive information into the spinal cord. This in vitro phenomenon, if representative of physiological responses, suggests that astrocytes may play a role in central processing of noxious input. The fact that astrocytes from rat cortex do not exhibit substance P-evoked prostanoid release provides further evidence for regional astrocyte heterogeneity.