Activity of dorsolateral prefrontal cortical neurons was examined in rhesus monkeys while they performed a spatial delayed-response task with delays of 2, 4, 8 or 12 s interposed between cue and response. Of the 600 neurons recorded for at least 10 trials under each delay condition, 95 displayed a pattern of discharge during the delay period which was significantly different from neuronal firing before or after this period. Changes in the duration of the delay elicit two distinct patterns of activity in these neurons: some (59/95, 62%) exhibit a fixed pattern of discharge regardless of the duration of the ensuing delay; others (31/95, 33%) alter their pattern of activity in relation to the temporal changes. Although both types of delay-related neurons display a variety of discharge profiles, more than half of each class exhibit their highest activity in the early part of the delay period. A related finding concerns a small subclass of spatially selective neurons which fire significantly more when the cue is presented on the left than on the right or vice versa. A striking 80% of these spatially discriminative neurons exhibit peak activity in the first few seconds of the delay period. These findings provide cellular evidence that (1) prefrontal neurons are responsive to temporal as well as spatial features of the delayed-response task; and (2) the involvement of a subset of these is particularly critical in the first few seconds of the delay. The latter finding emphasizes that prefrontal neurons may play an important role in the registration process of spatial memory.