Arnaud De Lie had been suffering since the Giro d'Italia began and it became too much to bear on Tuesday as the Belgian's race came to a premature end on the back half of stage 4.
The Lotto-Intermarché rider fell ill ahead of the Giro with a stomach bug that was blamed on cow manure on the roads of a race in Belgium the previous week, which he won.
De Lie was caught behind the late crash on the opening stage in Bulgaria but was in no shape to sprint for victory anyway, as was evidenced the following day when he suffered on the day's late climb and finished down in 155th place.
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He made the transfer from Bulgaria to Italy but his condition did not improve on the rest day, and he was dropped once again on stage 4. Most of the sprinters were in fact distanced on the category-2 Cozzo Tunno climb inside the final 50km of Tuesday's stage, but it was soon confirmed over race radio that De Lie had climbed into his team car and abandoned the race.
De Lie was thought to have become infected with campylobacter after winning the Famenne Ardenne Classic earlier this month. There were reports of cow manure on the route, with the rain soaking it across the roads and riders' wheels spraying it into the peloton.
Several riders fell ill, with reports of some requiring hospital treatment. Lotto Intermarché had to pull Liam Slock from their Giro squad, drafting in debutant Josh Giddings as a last-minute replacement. Milan Menten was also suffering with the same issue but continued fighting in the Giro for now.
And now the freak incident has resulted in their leading hope for a stage win having to head home.
"I felt OK until during the flight to Bulgaria, I felt myself getting worse and worse. I don't think I have ever felt this bad," De Lie said after the opening three stages.
De Lie will now turn his attention to the Tour de France. He was always set to make an early exit from the Giro to avoid the mountainous stages later in the race.
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