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Microbial variant forms whose cell walls are deficient may persist in vivo if environmental conditions are favorable. The significance of the variants in clinical disease states remain unclear. Quantitative in vitro antibiotic sensitivities of representative. L-forms are presented. Four patients witir chronic osteomyelitis are described. Material from their wounds grew Staphylococcus aureus on culture not in routine media but in hypertonic media. The organisms either were parent forms or L forms. None of these patients were receiving cell-wall-inhibiting antibiotics at the time of culture. Three of the four patients had metal implants. Despite the fact that the L-phase variants in these patients were derivatives of Staphylococcus aureus, a frankly purulent response was not seen.All patients with recurrent osteomyelitis with sterile drainage in the absence of antibiotic treatment, or whose wounds contain only unusual orgarnisms which may be saprophytes, should be routinely investigated for L forms.The possibility that wall-deficient variants derived from bacteria other than Staphylococcus aureus may play important roles in bone infections should be entertained. We have not been able to find such cases. However, sinc these variants may remain as persistent forms, periods of relative clinical quiescence may represent the ideal time for culture. Definite therapeutic recommendations depend on quantitative and qualitative studies of sensitivity to antibiotics. On the basis of our experience it would seem that more attenion should be paid to these bacterial forms in chronic bone infection.