Pituitary adenylate cyclase-activating peptide (PACAP) is present in the lungs, notably in their internal neuroendocrine system; however, its use is not clear. It was investigated for its possible ability to cause lung-liquid reabsorption around birth. Lungs from 31 late-term fetal guinea-pigs (at 60 ± 2 days of gestation) were supported in vitro for 3 h; lung-liquid movements were monitored by a dye-dilution method. Untreated control preparations (n = 9) produced fluid at 1.85 ± 0.40 mL·kg–1 body mass·h–1 (mean ± SD), with no significant change (ANOVA, regression analysis). Those given 10–8 M PACAP in the middle hour turned to reabsorption (n = 3) or reduced production markedly (n = 3) (average fall 84.4 ± 5.4%; significant at P < 0.001–0.0005); effects continued and increased after the PACAP was removed. Preparations given 10–9 M PACAP reacted similarly, but there was partial recovery after treatment (five reabsorbed, four reduced production; average fall 91.4 ± 14.3%; significant at P < 0.01–0.0005). Preparations given 10–10 M PACAP all reduced production, with partial recovery (average fall 43.5 ± 8.2%; significant at P < 0.005–0.0005). Preparations given 10–11 M PACAP showed little or no effect. The linear log dose–response curve became maximal at 10–9 M (r2 = 0.98; theoretical threshold 10–13 M). The results increase the likelihood that the neuroendocrine system is important in lung-liquid reabsorption, and suggest that PACAP could combine its relaxation of airways with lung-liquid removal, and therefore aid the first attempts of the newborn to breathe.