In order to characterize the epidemiological and clinical picture of post-streptococcal acute glomerulonephritis (PSAGN), a prospective study was designed to investigate all admissions to a general hospital of a local health service in Chile. The protocol included the investigation of previous streptococcal infections (SI), clinical symptoms and signs, socioeconomic situation (SES), throat and skin swabs for the isolation of group A beta-hemolytic streptococci, sequential determination of serum antistreptolysin O (ASO) titer, anti-DNAase B antibodies, and C3. During the 20 years studied, 926 cases were admitted (56% males). Incidence showed an endemic period (EP) 1980–1983, an epidemic outbreak (EO) 1984–1989, and a late period (LP) 1990–1999, with a rate per 100,000 inhabitants of 6.2, 13.2, and 1.7, respectively. The clinical picture was similar in the three periods. SES was homogeneous, with 80% of the population in low and middle-low categories. The average size of the family was 6.9 compared with 4.8 in the general population. Pyoderma was more frequent than pharyngeal infection, and more so during the EO. The isolation rate of group A beta-hemolytic streptococci from the pharynx was 20% compared with 60% from skin swabs. During EP, the most prevalent serotypes were T14-M0 and T1-M1 from the pharynx and TImp19-M0 from the skin. During EO, T14-M0 was more prevalent (30%). M or T classification was possible in EP and EO in 80%–85% of all strains isolated from the two locations. Significant titers for ASO and anti-DNAase B were found on admission: 55% and 75%, respectively. Both tests allowed identification of 100% of previous SI. In conclusion, the incidence of PSAGN had an uneven trend during the observed period. EO was mainly due to skin infection and a predominance of one serotype, T14-MO, was observed. After the EO, the yearly rate gradually decreased from 13.2 in 1988 to 0.0 in 1999, a rate similar to that of industrialized nations.