To assess prevention strategies for pneumococcal disease in Alaska, prospective surveillance during 1986-1990 identified 672 invasive pneumococcal infections, including 315 among Alaska Natives. Age-adjusted annual incidence was 74 per 100,000 for Alaska Natives and 16 per 100,000 for nonnatives. The annual incidence in Alaska Native children < 2 years old was 624 per 100,000; rates of 84 per 100,000 for meningitis and 290 per 100,000 for bacteremic pneumonia were 8-10 times higher than for other US groups. By age 75, cumulative incidence (7%) and mortality (1%) in Alaska Natives were almost 4 times higher than for nonnatives. Only 17% of Alaska Native adults with predisposing conditions and invasive infections previously received pneumococcal vaccine. For Alaska Natives, a proposed heptavalent conjugate pneumococcal vaccine will include serotypes responsible for 85% of invasive isolates from children < 2 years but only 32% of those from adults. The 23-valent polysaccharide pneumococcal vaccine, which contains > 94% of serotypes identified in Alaska Native toddlers and adults, should be used more widely.