It has recently been hypothesized that tail-skin temperature may exert a profound influence on the latency of the tail-flick response to radiant heat. Several recent reports in the literature urge investigators to assess tail temperatures concurrently when using the tail-flick test and to adjust the tail-flick latency by a coefficient when a change in tail temperature is detected. Because much of the supporting evidence of this hypothesis was strictly correlational, the purpose of the present study was to determine whether tail-skin temperature is an important factor contributing to the latency of the tail-flick response to radiant heat. The effects of a series of pharmacological and non-pharmacological manipulations on tail-skin temperature and response latencies were assessed using either a low-intensity or high-intensity tail-flick stimulus. In addition, colonic temperature was evaluated. None of the drug treatments yielded a significant correlation between tail temperature and tail-flick latency. Of the seven drugs tested, only mecamylamine produced a consistent change in tail-skin temperature. Although mecamylamine significantly elevated tail temperature by more than 2°C, it failed to alter response latencies. Similarly tail submergence into 5°C water for 10 sec led to profound decreases in tail temperature ranging from −6.5 to −7.6°C while producing only minimal increases in tail-flick latency. Conversely, submerging the tail in 38°C water or placing the animals over a heating pad maintained at 38°C increased tail temperatures at least 2°C without affecting response latencies. Inverse correlations were found between tail-flick latency and colonic temperature after morphine, Δ9-tetrahydrocannabinal (Δ9-THC), and nicotine administration; however, these relationships do not appear to be causal. Sodium barbital produced far more hypothermia than any other agent, but did not produce any antinociception. Moreover, placing subjects in heated cages increased tail-skin temperature between 2 and 4°C and blocked the hypothermic effects of morphine and Δ9-THC without reducing the antinociceptive potencies of these agents. These findings indicate that tail-skin and core temperatures have a negligible influence on the tail-flick response. We conclude that monitoring tail-skin or core temperatures when employing the tail-flick test is unnecessary and altering tail-flick latencies to account for changes in tail temperature is unwarranted.