This article evaluates the evidence to support the use of biochemical measurement of significant reduction (SR) rates among pregnant smokers as a new behavioral indicator of "harm reduction" (HR). The results of four studies--three randomized patient education clinical trials of pregnant smokers (Trials I, II, and III) and an epidemiological study (Study IV)--are presented. Among Trial I, II, and III cohorts of pregnant smokers, control group SR rates of 7% (I), 9% (II), and 20% (III) were increased among experimental groups to 17% (I), 18% (II), and 32% (III) by the same patient education methods. Analyses of infant birthweight data in Study IV found that a patient SR rate representing a 50% or more decrease between a baseline and follow-up test was associated with an increase in adjusted birthweight of 92 grams.