The crab Chasmagnathus granulatus reacts to a shadow passing overhead (a danger stimulus) with an escape response that habituates quickly and for at least 5 days. Recently, it has been reported that cycloheximide (CY) disrupts this long-term habituation and the corresponding context memory. In the present article, experiments with CY and an inhibitor of RNA synthesis, actinomycin-D (ACT), were parallelly conducted. An injection of CY (20 micrograms) or ACT (0.62 microgram) reduced the incorporation of [14C]-aminoacid into cerebral plus thoracic ganglia by 80% for 2 h and 59.7% for 1 h, respectively, but no inhibition was found at 24 h. Both ACT (0.62 microgram) and CY (20 micrograms) administered immediately after training (15 trials with the danger stimulus) impaired either long-term habituation or context memory when tested at 24 h. Because ACT and CY have in common only their direct or indirect inhibitory effect on protein synthesis, this finding is considered as an additional evidence that long-term memory in Chasmagnathus requires de novo protein synthesis. However, pretraining ACT or CY impaired context memory at 24 h but not long-term habituation. Such a disparity is explained by an unspecific attenuating effect upon the response, attributed to drug x training interaction. Neither ACT nor CY affected short-term habituation.