The irritable male syndrome (IMS) is a behavioural state of nervousness, irritability, lethargy and depression that occurs in adult male mammals following withdrawal of testosterone (T). The negative mood state has been described in men following withdrawal of androgens and is a striking feature in male seasonally breeding mammals associated with the end of the mating season. The Soay ram provides an animal model for IMS. Rams exposed to alternating 16-week periods of long and short days inactivate the reproductive axis in response to the switch to long days; the rapid decrease in T secretion provokes the symptoms of IMS. The animals appear agitated and fearful, and the incidence of physical wounding owing to fractious inter-male fighting peaks at this time. Androgen and oestrogen receptors expressed in cells in the preoptic area and ventromedial/arcuate nuclei appear to relay the effects of T on behaviour and gonadotrophin secretion, and melatonin receptors expressed in the premammillary area relay the effects of melatonin/photoperiod. Changes in the activity of hypothalamic opioidergic, dopaminergic and serotonergic neural networks may dictate the interactive effects of T and photoperiod. The working hypothesis is that IMS is a transition state associated with low hypothalamic amine levels triggered, in part, by the withdrawal of opioid peptides.