Nauseaandvomiting induced bychemotherapy isa variable responserelated tothenatureandintensity oftreatment and patient susceptility. Themechanism whereby chemotherapy evokes nausea andvomiting isuncertain butrecently, the ability of5-HT3receptor antagonists toantagonise chemotherapy induced emesis inanimals (Costall etal., 1986; Miner & Sanger, 1986) andman (Cunningham etal., 1987; Leibundgut & Lancranjan, 1987; Krisetal., 1989) hasfocused interest on theroleof5-hydroxytryptamine (5-HT). Ithas beenhypothesised thatemetogenic chemotherapeutic agents may release 5-HTtotrigger theemetic reflex via5-HT3 receptors located atcentral sites or on theafferent vagus nerve(Andrews etal., 1988; Hawthorne etal., 1988; Higgins etal., 1989). 5-HTisfoundinhighconcentration inthe enterochromaffin cells andplatelets anda release of5-HT fromsuchsites wouldbeexpected toelevate thecirculating levels of5-HT(Verbeuren, 1989). Thepresent studies were designed toinvestigate whether plasma 5-HTlevels areincreased during chemotherapy inpatients receiving thepotent emetogencisplatin. Tenmalepatients agedbetween 20and39years(median 30years) undergoing cisplatinum-containing cytotoxic therapy formetastatic germ cell tumourofthetestis (teratoma eight patients, seminoma twopatients) were studied during thefirst 24hofa 5-day courseoftreatment. Commonlyused schedules oftreatment were employed, mainlytheBEP regime (bleomycin, etoposide andcisplatinum). Allpatients received pre-chemotherapy antiemetics. Although there were minorvariations intheantiemetic regime tosuit individual patients, thecommonly usedschedule was lorazepam 2mg, metoclopramide 1Omg anddexamethasone 8mg, allgiven intravenously athour0,together withfurther dosesof appropriate drugs on demandinthecaseofnauseaorvomitingdeveloping after theinitiation oftherapy. Indwelling cannulae (standard 22gaugeneedle or a 22 gaugeVenflon) were inserted intoa surface veinon the dorsumofthehandandsealed withattachable rubber caps. Intravenous cisplatin (20mg m-2)was administered in1 litre ofnormalsaline over4h viaa surface veinoftheopposite forearm using an IMED 960volumentric infusion pump. Bloodsamples weretakenimmediately before theinfusion of cisplatin andthenat2,4,6,8,16and24hafter thestart of treatment. Eachsampling involved theremovalof5 ml of bloodprior tothecollection ofa 2.7mlsample intoa 2.7ml monovettevial(Startedt). The contentsofthevialwere immediately mixed.Within5-15minof collection 1ml aliquots ofthesamples were removedandcentrifuged at 15,000 g for3minto separate thebloodcells fromthe plasma. Aliquots of200jil ofplasma were thenremoved, immediately frozen andstored inliquid nitrogen before analysis. Fortheextraction of5-HT,8 of20mg ml-'