Hemiscorpius lepturus (H. lepturus), found in south-western areas of Iran and south of Iraq, is considered to be the most dangerous scorpion in the region, and poses a significant risk to the health of the indigenous population due to the unique, clinical manifestations associated with its sting.. In the present study, 36 patients from the Khuzestan province in the southwest of Iran, displaying varying degrees of envenomation following an H. lepturus scorpion sting, were admitted to hospital. Serum levels of interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-8 (IL-8) and tumour necrosis factor-α (TNF-α) were measured using double-ligand, enzyme-linked, immunosorbent assay (ELISA) kits, and were compared with 30 healthy controls and ten age-matched patients stung by the Mesobuthus eupeus (M. eupeus) scorpion, a less dangerous species that produces primarily neurotoxic manifestations. Blood samples from M. eupeus and H. lepturus victims were taken on admission, and from H. lepturus-stung patients six hours after serotherapy with multivalent anti-venom. When compared to healthy volunteers, with the exception of TNF-α, significantly higher serum cytokine levels were measured in patients following M. eupeus envenomation. However, all three groups of H. lepturus-stung patients showed significantly, and in a severity-related manner, higher mean values for all the interleukins that were measured, including TNF-α, when compared with M. eupeus-stung cases. Six hours after serotherapy, there was a greater reduction in cytokine and TNF-α levels in patients classed as having mild symptoms, in comparison with patients classed as having moderate to severe symptoms. The results of the present study suggest that, unlike M. eupeus, the toxic manifestations observed following being stung by H. lepturus are associated with increased serum TNF-α levels and correlate positively with the clinical severity of the symptoms. Furthermore, serotherapy is only effective when administered to mild cases of H. lepturus scorpion envenomation.