Opiates modulate nociception in vertebrates. This has also been demonstrated in a number of invertebrate models. Herein, the effect of the opiate morphine and opioid neuropeptides Endomorphin 1 and 2 on the thermal avoidance (Tav) behavior of Caenorhabditis elegans is explored. Adult wild-type C. elegans N2 were collected from NGM plates using M9 buffer and exposed to morphine and endomorphine 1 and 2 in concentrations between 10(-8) and 10(-4) M (2.5 pmol/mg to 25 nmol/mg) for 30 min and tested for Tav. The opioid receptor antagonists Naloxone and CTOP were tested in combination with the drugs. Forty-seven percentage of the morphine exposed worms exhibited a class I response versus 76% of the control group (P < 0.001). Endomorphin 1 and 2 also caused a statistically significant reduction in class I responses, 36 and 39%, respectively. These effects were reversed with Naloxone and CTOP. Thermonocifensive behavior in C. elegans is modulated by opioids.