McLellan TM. Chemical-biological protective clothing: effects of design and initial state on physiological strain. Aviat Space Environ Med 2008; 79:500–8. Purpose: This study examined whether heat strain during low states of chemical and biological protection (CB_low) impacted tolerance time (TT) after transition to a high state of protection (CB_high) and whether vents in the uniform reduced heat strain during CB_low and increased TT. Methods: There were eight men who walked at 35°C in CB_low and then transitioned to CB_high. Subjects wore fatigues in CB_low with an overgarment during CB_high (F+OG) or a new 1-piece (1PC) or 2PC uniform throughout CB_low and CB_high. One condition also tested opened vents in the torso, arms, and legs of the 2PC uniform (2PC_vent) during CB_low; these vents were closed during CB_high. Also worn were fragmentation and tactical vests and helmet. Results: Heart rates were reduced significantly during CB_low for F+OG and 2PC_vent (114 ± 13) vs. 1PC and 2PC (122 ± 18). Rectal temperature (T_re) increased least in CB_low for F+OG (0.86 ± 0.23°C) and was significantly lower for 2PC_vent (1.02 ± 0.25°C) vs. 2PC (1.11 ± 0.27°C). T_re increased rapidly during CB_high for F+OG, which had the shortest TT (40 ± 9 min). Increased thermal strain during CB_low for 1PC negated its advantage in CB_high and TT (46 ± 21 min) was similar to F+OG. Differences in T_re between 2PC and 2PC_vent remained during CB_high where TT was increased during 2PC_vent (74 ± 17 min) vs. 2PC (62 ± 19 min). Conclusions: It was concluded that heat strain during CB_low impacted TT during CB_high, and use of vents reduced heat strain during CB_low, thereby increasing TT.