Finnish postmortem toxicology data from 1995 to 2002 was analyzed to obtain improved estimates of fatal toxicity indices for the newer antidepressants and to evaluate their interaction with alcohol. Altogether 284 fatal poisonings were attributed to 12 different newer antidepressants. Venlafaxine, mianserin, moclobemide, and mirtazapine were responsible for significantly more deaths than expected from their sales. Their fatal toxicity indices were higher than those of selective serotonin reuptake inhibitors (SSRIs) but lower than those of tricyclic antidepressants. In fatal poisonings involving alcohol in combination with venlafaxine, mianserin, moclobemide, or mirtazapine, the median blood alcohol concentration (BAC) ranged from 2.35 to 2.7 mg/g, whereas in those involving alcohol in combination with citalopram or fluoxetine the median BAC was 2.9 and 3.4 mg/g, respectively. The BAC was significantly lower in venlafaxine-related deaths than in those involving fluoxetine or citalopram. We conclude that among the newer antidepressants differences are present both in toxicity and in interaction potential with alcohol. The SSRIs appear to present a low risk of fatal poisoning when taken alone or in combination with alcohol, whereas venlafaxine is associated with an elevated risk.