5-Hydroxytryptamine (5-HT, 0.01-100 microM) and 5-carboxamidotryptamine (5-CT, 0.001-10 microM) produced dose-related relaxations in strips cut from monkey popliteal lymph nodes precontracted with a perfusion of Krebs bicarbonate solution containing 80 mM KCl. These 5-HT agonists caused no significant effect on the basal tone of the lymph node strips. The 5-HT-induced relaxation is competitively antagonized by pretreatment with a selective 5-HT1-like receptor antagonist, methiothepin (0.01-0.1 microM). Schild plot analysis showed that the pA2 value and slope of methiothepin against 5-HT were 8.80 +/- 0.11 and 0.99 +/- 0.07 (n = 6), respectively. Pretreatment with methysergide (0.01-0.1 microM) significantly attenuated the 5-HT-induced relaxation of the strips. On the other hand, treatment with ketanserin (0.01-0.1 microM) and ICS-205-930 (0.01-0.1 microM) caused no significant effect on the 5-HT-or the 5-CT-induced relaxation. The 5-HT-induced relaxation was significantly reduced by 10 microM NG-monomethyl-L-arginine, which was reversed by 1 mM L-arginine. The relaxation in the lymph node strips was also significantly reduced by treatment with 10 microM methylene blue but not with 30 microM aspirin. These results suggest that 5-HT1-like receptors exist in the monkey popliteal lymph nodes. Stimulation of these receptors produces an endogenous nitric oxide (NO)-dependent relaxation in lymph node smooth muscle through an activation of cytosolic guanylate cyclase in the cells.