The purpose of this study was to examine the relationship of early initiation of sex, drug-use, drug-trafficking, and sensation-seeking among urban, African-American adolescents. A longitudinal follow-up of 383 youth ages 9 to 15 years at baseline over four years with serial risk-assessments was used. Sexual experience and several drug-related risk behaviors increased significantly during the four-year study interval. Sensation-seeking scores were higher after the baseline assessment among youth reporting tobacco, alcohol, and marijuana use and were higher, both at baseline and through several follow-up assessments, among youth reporting drug-selling and sexual activity. At baseline, the correlations among drug-related risk behaviors were all strong, except those between initiation of sex and drug-related risk behaviors. However, over time, early initiators of sex were significantly more likely to report involvement in substance use and drug-delivery/sales than were late initiators. Youth reporting repeated involvement in drug-related activities were more likely to report intensive sexual involvement than they were to report experimental sex or no sex. Sensation-seeking scores were lower among youth reporting no involvement in risk behaviors. However, scores did not differ between youth exhibiting experimental behavior compared to youth demonstrating repeated risk involvement. These results support the need for alternative experiences for youth exhibiting high levels of sensation-seeking and the need for early drug/sexual risk prevention programs.