Medvedev, representing Ukraine along with his sister, Natalia Medvedeva, hobbled around the court as his country were knocked out in the first round by unseeded Austria.
The 19-year-old world No 6 was beaten 4-6, 6-2, 6-1 by Alex Antonitsch and hurried away to seek medical advice.
'From the second set onwards, the pain was getting worse and worse,' said Medvedev, who received treatment for an inflamed knee muscle in Florida before Christmas.
The Australian Open has already lost several leading attractions, notably Andre Agassi who has had wrist surgery and Boris Becker, whose wife is pregnant. Michael Chang, John McEnroe, Martina Navratilova and Jennifer Capriati have also decided not to compete.
Medvedeva was beaten 7-6, 6-3 by Judith Wiesner in the opening singles, and the pair eventually scratched from the 'dead' doubles rubber to give Austria a 3-0 winning margin.
The organisers experienced a further disappointment when the player on stand-by, Britain's Andrew Foster, could not be found in time to replace Medvedev. His coach, Andrew Jarrett, was hastily drafted in to partner Clare Wood in an exhibition doubles match against the Austrian pair.
For the first time at a major tournament, all line calls are being made by machines instead of people.
'The machine made three bad calls today,' Medvedev said. 'It's not fair to fire all the people. Human beings are better than machines.' Antonitsch felt the system made the game 'more boring'.
'You feel like you're playing video games. . . there's no one to argue with,' he complained. 'Somehow it's part of the game questioning calls. I'll have to start talking to the machine.'
From the chair, the innovation was viewed more positively. Jane Tabor, the British umpire, admitted the system, which she operated with a hand-held computer, required extra concentration.
'There's a lot to think about, but the accuracy is superb,' she said. 'You just have to train yourself to do a few extra things. It is a comfortable feeling that you're not going to get any queried calls.'
Tabor conceded there had been teething problems, mostly involving the handset which has to be activated before each point. One of the buttons jammed at one stage and the system was turned off for the final doubles rubber after several inadvertant bleeps.
At one stage, Medvedev also did his good-humoured best to sabotage the whole operation by unplugging the apparatus.