Abstract This study investigated gestational regulation of transient receptor potential canonical (TrpC) proteins, putative calcium entry channels in human myometrium, and the potential modulation of TrpC expression by IL–1β, a cytokine implicated in labor. Total RNA and proteins were isolated from myometrial biopsies obtained from NP women, pregnant women at term not in labor (TNL), or term active labor (TAL) and from primary cultured human myometrial smooth muscle cells incubated with IL–1β or IL–1β with or without nimesulide. Semiquantitative RT-PCR demonstrated significant up-regulation of TrpC1 in TAL and TNL (P ≤ 0.01) and TrpC6 (P ≤ 0.01) and TrpC7 (P ≤ 0.05) in TAL samples. TrpC3 and TrpC4 mRNA expression was unaffected. Western blot demonstrated significant up-regulation of TrpC1 in TAL and TNL (P ≤ 0.05) and TrpC3 (P ≤ 0.01), TrpC4 (P ≤ 0.05), and TrpC6 (P ≤ 0.01) in TAL samples. IL–1β did not alter TrpC1, 3, 4, 6, or 7 mRNA expression; but IL–1β exclusively up-regulated TrpC3 protein expression (P ≤ 0.05). TrpC3 up-regulation was unaffected by cyclooxygenase blockade. These data demonstrate physiological regulation of TrpC mRNA and protein and suggest an important role for TrpC proteins in human myometrium during labor.