Suicides involving alcohol or other substance dependence have been studied in male-dominated populations. We studied male and female suicide victims with DSM-III-R psychoactive substance dependence (PSD) separately in a nationwide psychological autopsy study in Finland. The subjects were substance-dependent males from a systematic random sample and all substance-dependent female suicide victims from the total population of suicides committed over a 1-year period in Finland. Comparisons by sex and age were made, and two logistic models were created predicting sex. Females were more likely to have abused or been dependent on prescribed medication. Female victims aged 40 years or less had a relatively high frequency of borderline personality disorder (BPD), frequent previous suicide attempts, and suicidal communication, whereas older females were more like older males. The onset of a comorbid axis I disorder preceded substance dependence more often among females. Male and female substance-dependent suicide victims differ in a number of characteristics, including previous suicidality, age-related variation in personality disorders, and type of substance used. Findings from studies of predominantly male substance-dependent suicide victims cannot necessarily be generalized to females.