The transient receptor potential (TRP) channels are important membrane sensors, responding to thermal, chemical, osmotic or mechanical stimuli by activation of calcium and sodium fluxes. In this study, three distinct TRP-channels were detected and their role established in mediating cytosolic calcium ([Ca²⁺]_c) response in tumor-derived SW982 synoviocytes and primary cultures of human synovial cells from patients with inflammatory arthropathies. Using fura-2 ratio measurements while incubating cells in a temperature regulated chamber, significant [Ca²⁺]_c elevation was elicited by rapid changes in bath temperature, application of TRPV1 receptor agonists, capsaicin and resiniferatoxin, or a cold receptor stimulator, icilin. No changes in [Ca²⁺]_c were produced by menthol. Temperature thresholds for calcium response were determined to be 12 ± 1°C for cold and 28 ± 2 °C for heat activation. Temperature increases or decreases beyond these thresholds resulted in a significant rise in the magnitude of [Ca²⁺]_c spikes. Observed changes in [Ca²⁺]_c were completely abolished in Ca-free media and thus resulted from direct calcium entry through TRP channels rather then by activation of voltage-dependent calcium channels. Two heat sensitive channels, TRPV1 and TRPV4, and a cold-sensitive channel, TRPA1, were detected by RT-PCR. Minimal to no mRNA for TRPV3 or TRPM8 was amplified. The RT-PCR results support the data obtained with the [Ca²⁺]_c measurements. We propose that the TRP channels are functionally expressed in human synoviocytes and may play a critical role in adaptive or pathological changes in articular surfaces during arthritic inflammation.