L-phase bacteria are bacterial variants produced by adverse conditions in the environment. Although variant growth may be perpetuated for generations, the changes are not of genetic origin, but due solely to the environment which causes damage to the bacterial cell wall. Since the structure of Gram-positive and Gram-negative cell walls is fundamentally different, the degraded variant which will occur in each case will also be different. Such variants are seldom detected in routine diagnostic laboratories because they will not grow on normal media, as their optimal conditions of growth are changed. L-phase variants bear a strong resemblance to the mycoplasmas; both are resistant to penicillin, both lack characteristic bacterial cell wall constituents, and their colonial and cellular morphology are similar. Since the conditions for mycoplasma cultivation are, at this time, more clearly understood, they provide useful models for handling fragile L-phase organisms. L-phase bacteria may be readily produced in vitro by the action of penicillin, and it is theoretically possible for conversion to occur in vivo just as readily during phagocytosis, by the action of bacteriophage, antibiotic therapy, and other defence mechanisms of the host. In the clinical field, the most difficult problem is the assessment of the significance of the isolation of L-phase bacteria in the individual case because they have not been observed with certainty in the pathological process. It is probable that such organisms may be clinically significant in cases of chronic and recurrent infection, since these bacteria will survive the defence mechanisms of the host which are largely directed at the cell wall.