Prospective analysis of the etiology of community-acquired pneumonia in 209 inpatients (mean age 56.2+/-11.2 years) was performed at the Lung Hospital of Tartu University, Estonia. Majority of the patients (87.6%) had at least one significant modifying or risk factor and 30.6% had severe community-acquired pneumonia. Streptococcus pneumoniae, beta-hemolytic streptococci, Klebsiella pneumoniae, and Moraxella catarrhalis were the most frequent pathogens (22.0, 12.2, 11.4, and 10.2%, respectively). Combined etiology was detected in 17.2%. Gram-negative pathogens prevailed over gram-positives and were significantly more frequent in patients aged > or =60 years (p=0.002) as in those with underlying diseases (p=0.01). An age of > or =60 years and previous antibacterial therapy were significant risk factors for Klebsiella pneumoniae as a pathogen (p=0.005 and p=0.002, respectively). Susceptibility of Streptococcus pneumoniae to penicillin, erythromycin, and doxycycline was 79.5, 90.2, and 100%, respectively, whereas all penicillin-resistant isolates were cefuroxime- and ceftriaxone-susceptible. Klebsiella pneumoniae was 100, 88.5, 84.2, and 81.8% susceptible to ceftazidime, gentamicin, ampicillin-sulbactam, and ciprofloxacin, and Moraxella catarrhalis was 100, 100, 100, 93.8, and 93.3% susceptible to ampicillin-sulbactam, cephalexin, ceftriaxone, ciprofloxacin, and erythromycin, respectively. In conclusion, Streptococcus pneumoniae, Moraxella catarrhalis, and Klebsiella pneumoniae were the major pathogens of community-acquired pneumonia in Southern Estonia. Although gram-negatives were more prevalent, the major pathogens were favorably susceptible without a noticeable cross-resistance. Nevertheless, improved surveillance studies are needed because of a pressure for the rise in antibiotic resistance in the society.