The potential application of mesoionic compounds as chemotherapeutic agent has long been recognized, for example 4-phenyl-5-[4-nitrocinnamoyl]-1,3,4-thiadiazolyl-2-phenylamide cloride (MI-D) has in vitro activity against human melanoma cells (Senff Ribeiro et al., British J Cancer, 91, 297, 2004), and in vivo and in vitro against murine melanoma (Senff-Ribeiro et al., Melanoma Res. 13, 297, 2003). Applied in rats, it shows an antiinflammatory effect, suggestive of cycloxygenase 2 (COX-2) inhibition (Cardoso et al., Drug Develop. Res. 61, 207, 2004). In melanoma tumors, COX 2 is a constitutively expressed enzyme, which seems to be involved with the regulation of invasiveness. The present study is to verify if the COX 2 of human melanoma cells would be a target of MI-D. The human melanoma lineages MEWO, MEL-85 and SK-MEL were used. For viability assays and prostaglandin production, cells were grown in RPMI medium supplemented with 10 % (MEWO and MEL-85) or 15% (SK-MEL) of bovine fetal serum. The cells (2x10⁵) were plated (12 well plates) and after 24 h were exposed to MI-D (2.5; 5; 10 e 25 mmol.L^-1)  by 1, 3 and 6 h. The cell viability was evaluated with Trypan blue. To evaluate the effect of MI-D on the production of PGE₂, cells were treated (2 h) with 10 mmol.L^-1 MI-D and then exposed (1h) to a medium containing arachidonic acid (20 mmol.L^-1). The PGE₂ concentration in supernatants was determined using the kit  “Prostaglandin E₂ EIA Monoclonal” (Cayman Chemical Company, INC). Controls were treated with 0,12% de DMSO.  Under these conditions, MI-D did not affect cell viability, except for MEL-85, which gave rise to loss of adherence and rounded morphology (at 10 and 25 mmol.L^-1 MI-D). All lineages produced PGE₂, this for 2.10⁵ cells being for MeWo 2,143 (⁺ 46) pg/mL, SK-MEL, 1,597 (⁺ 144) pg/mL and MEL-85 350 (⁺ 46) pg/mL. MI-D lowered of the production of PGE₂ in MEWO (57%) and SK-MEL (37%). No effect was observed for MEL-85, showing the differences of sensitivity between lineages. Senff-Ribeiro et al (2004) showed that MI-D interferes with the adhesion of MEL-85 cells to matrix elements, when exposed (2 h) to low concentrations. COX2 seems to be a target for MI-D; but it was not possible with the present data to establish a relation between the decreased PGE₂ production and the antitumoral effect of MI-D, suggesting that other factors besides inhibition of COX2 are involved.