ABSTRACT. A comparative analysis of low linear energy transfer (LET) c-radiationinduced damage in the lymphatic tissue of a tropical seasonal breeder, Indian palm squirrel (Funambulus pennanti), during its reproductively active phase (RAP) and inactive phase (RIP) was performed with simultaneous investigation of the effects of long-term melatonin pre-treatment (100 mg/100 g body weight). A total of 120 squirrels (60 during RAP and 60 during RIP) were divided into 12 groups and sacrificed at 4, 24, 48, 72 and 168 h following 5 Gy c-radiation exposure; control groups were excluded from exposure. Total leukocyte count and absolute lymphocyte count (ALC) and melatonin only of peripheral blood, stimulation index, thiobarbituric-acid-reactive substances (TBARS) level, superoxide dismutase (SOD) activity, and the apoptotic index of spleen as analysed by terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP) nick-end labelling (TUNEL) noted at observed time-points were significantly reduced in melatonin pre-treated groups during RAP and RIP. Long-term melatonin pretreatment mitigated radiation-induced alterations more prominently during RIP, as assessed by ALC, TBARS, SOD, TUNEL and caspase-3 activity, at some time-points. Our results demonstrate an inhibitory role of melatonin on caspase-3 activity in splenocytes during RAP and RIP following c-radiation-induced caspase-mediated apoptosis. Hence, we propose that melatonin might preserve the viability of immune cells of a seasonal breeder against background radiation, which is constantly present in the environment. The increasing number of personnel working with radiation, together with the development of nuclear weapons, stimulated an interest in the study of radiation effects on immunity. Radiation-induced injury due to free radicals and reactive oxygen intermediates (ROI) could impair specific immune responses. Besides ultraviolet (UV) radiation, a common environmental stressor that influences animals [1] and humans [2], X-rays and c-rays are readily available from natural and artificial sources [3][4][5]. The earth and all living things are constantly bombarded by the background radiation present in soil, water, earth and vegetation [6,7]; one of the major contributors to background radiation is c-radiation [8,9]. Funambulus pennanti (Indian tropical palm squirrel), a photoperiodic seasonal breeder that lives close to human populations, is exposed daily to solar radiation and UV as well as to background radiation. Immune functions of this squirrel are always under the effect of environmental and biotic factors, such as ambient temperature, food availability, shelter, rainfall, humidity and other stressful conditions, with hormonal variations in different seasons. As F. pennanti is sensitive to seasonal changes and stressors, it is a suitable model for studying high-dose cradiation effects on the immune function under seasonally recurrent stressors. Reports regarding the destructive effect of low linear energy transfer (LET) ionising rad...