Reflex responses and neuronal excitation elicited by noxious stimuli applied to a given body site can be inhibited by application of noxious stimulation to another, even distant body region. Such heterotopic noxious stimulation (HNS) has been proposed to act via 'diffuse noxious inhibitory controls' (DNIC) which involve supraspinal components. The so-called on-cells of the rostral ventromedial medulla (RVM) in rats are thought to facilitate nociceptive transmission. Experimental manipulations that inhibit on-cells also inhibit withdrawal reflexes and nociceptive thalamic responses. In the present study on-cell activity was recorded in relation to the tail flick (TF) elicited by noxious heat applied to the tail both before and during either immersion of a paw in water above 56 degrees C or application of strong pinch to various body regions. Such HNS elicited strong activation of on-cells, followed by depression even when HNS continued. When this depression was intense, tail-heating failed to elicit vigorous on-cell firing, and TF was retarded or abolished. These results are compatible with the hypothesis that antinociception elicited by HNS involves depression of on-cell firing and hence lack of facilitation of nociceptive transmission.