Gender related variation in the molecular composition of venoms and secretions has already been described for some animal species, and there are some evidences that the difference in the toxin profile among males and females may be related to different physiopathological effects caused by the envenomation by either gender. In order to investigate whether this same phenomenon occurs to the toadfish Thalassophryne maculosa, we have compared some biological and biochemical properties of female and male venoms. Twelve females and 13 males were captured in deep waters of the La Restinga lagoon (Venezuela) and their venom collected from the spines. After protein concentration evaluation, the pooled venoms of females and males were fractionated by analytical HPLC System, analyzed by SDS-PAGE, assessed for induction of toxic activities in Swiss mice (nociception, edema, vascular permeability, necrosis and induction of cellular migration in the paw) and analyzed by LC-MS. Besides the anatomical differences, it could also be observed that molecular differences exist between the genders. Protein content is higher in males than in females (3.9 mg/ml vs 1.7 mg/ml; respectively), which may be associated to an apparent higher complexity of the male venom. It is also noteworthy that the LC-MS profile of the venoms showed that, at least three components (present in two peaks) are only present in males, namely proteins bearing molecular masses of 15135 and 15633 at RT 15,5 min and one peptide of 5066 Da at RT 13.5 min being the peaks not detected in the female venom. In vivo studies showed that mice injected with male venoms presented higher nociception when compared to those injected with female venoms, and both venoms induced migration of macrophages into the paw of mice. On the other hand, mice injected with female venoms had more paw edema and extravasation of Evans blue in peritoneal cavity than mice injected with male venoms. Finally, we observed that the female venoms had more capacity for necrosis induction when compared with male venoms (6.11 ± 0.85 mm² vs 3.41 ± 0.42 mm²). These results suggest that there are different toxins involved in the nociception and edema induced by T. maculosa venom. Furthermore, the presence of exclusive toxins in the male venoms could be related with the largest capacity of nociception induction, and the severity of the lesion characterized by necrosis development can be related with the poisoning for female specimens. SUPPORTED by FAPESP