Background: Electroconvulsive therapy is an effective therapy of depression. We hypothesized that the beneficial effects are mediated partly by decreased serotonin receptor availability in the cortex. Aims: We used positron emission tomography with the serotonin 5HT_2A receptor radioligand [¹¹C]MDL100,907 to determine serotonin receptor availability in response to electroconvulsive stimulation (ECS). Methods: Seven Göttingen minipigs were deeply anaesthetized and imaged at baseline before the onset of ECS, and at 1–2 and 8–10 days after the end of a clinical course of ECS, consisting of 10 sessions over 3.5 weeks, and post-ECS values were compared to baseline. One additional minipig was anaesthetized over 10 sessions without ECS, as a control. We analysed images with the Ichise model for binding in cortex and hippocampus, followed by whole-brain analysis by statistical non-parametric mapping. Results: We found significantly increased binding potential of [¹¹C]MDL100,907 in the cortex and hippocampus 1–2 days after ECS, consistent with increased serotonin receptor availability compared to baseline. By 8–10 days after the final ECS, the average tracer binding had returned towards baseline. However, we also found significantly decreased tracer binding in the subcortical regions of olfactory bulb, pons, thalamus and striatum. Conclusions: With ECS, minipigs, unlike primates but like rodents, have higher availability at cortical and hippocampal 5HT_2A receptors. Decreased tracer binding is consistent with reduced serotonin receptor availability as a differential effect of ECS on 5HT_2A receptors in subcortical regions of minipig brain.