The National Survey on Drug Use and Health (NSDUH) includes questions to assess serious psychological distress (SPD) and substance use. SPD is an overall indicator of nonspecific psychological distress. This report examines serious psychological distress and substance use among young adult males aged 18 to 25, a relatively understudied group with respect to mental health issues. All findings are annual averages based on combined 2002, 2003, and 2004 NSDUH data. An estimated 10.3% of males aged 18 to 25 (1.6 million persons) experienced serious psychological distress during the past year. Divorced or separated males aged 18 to 25 (20.9%) were more likely to have experienced serious psychological distress during the past year than those who were married (7.3%) or never married (10.5%). Males aged 18 to 25 with serious psychological distress during the past year were more likely than those without past year serious psychological distress to have engaged in heavy alcohol use (27.2% vs. 20.7%), binge alcohol use (56.7% vs. 49.9%), and illicit drug use (35.6% vs. 22.1%) in the past month. (Contains 3 figures and 6 endnotes.)