The objective of this study was to investigate the observation that patients with pneumonia due to penicillin-non-susceptible pneumococci (PNSP) in many instances present with milder disease than patients with pneumonia caused by penicillin-susceptible pneumococci (PSP) and to compare the cost of treatment. The clinical data, APACHE II score and laboratory features of hospitalized adults with pneumonia caused by PNSP or PSP were compared, along with antibiotic and hospital costs. Each patient with PNSP pneumonia (n = 36) was matched to a control with PSP pneumonia of the same age and gender. There was no difference in smoking history, but PNSP pneumonia patients had received prior antibiotics more frequently (p < 0.007). The mean APACHE II score was not different, but when broken down into acute vs. chronic scores those with PSP pneumonia had a significantly higher acute score (p = 0.005). Bacteraemia was present in 9 of 31 (29%) patients with PSP compared to 2 of 25 (8%) with the PNSP pneumonia (p = 0.09). The majority of isolates in the PNSP group were of serotype 6B (minimum inhibitory concentration range 0.125-2.0 mg/l), whereas serotypes 7, 9, 14, 18 and 19 were noted among the 9 PSP isolates. Compared with the control group, patients with the PNSP strains had a significantly longer hospital stay, 26.8 vs. 11.5 days (p = 0.001) and higher average antibiotic cost, $736 vs. $213 (p < 0.0001). In conclusion, pneumonia in adults caused by PNSP is associated with a milder clinical presentation than infection caused by PSP, suggesting either that resistance carries a price or that the serotypes of PNSP are less virulent. Pneumonia due to PNSP resulted in increased cost because of prolonged hospitalization and the use of more expensive antibiotics.